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Blood Biopsy Reveals Unique, Targetable Genetic Alterations in Patients with Rare Cancer – UC San Diego Health

Using fragments of circulating tumor DNA in blood, University of California San Diego School of Medicine researchers were able to identify theoretically targetable genetic alterations in 66 percent of patients with cancer of unknown primary (CUP), a rare disease with seven to 12 cases per 100,000 people each year.

In order to plan treatment for cancer in general, physicians first attempt to pinpoint the primary cancer where the tumor first developed. In CUP, despite its spread throughout the body, the origin remains unknown, making treatment more difficult. The current standard of care is platinum-based combination chemotherapies with a median survival time of six to eight months.

Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health.

In a study published in the journal Cancer Research on August 15, researchers report that by sequencing circulating tumor DNA (ctDNA) derived from blood samples in 442 patients with CUP, they were able to identify at least one genetic alteration linked to cancer in 290 66 percent of patients. Researchers used a screening test developed by Guardant Health that evaluates up to 70 genes. Based on known carcinogenic mutations, 99.7 percent of the 290 patients who had detectable tumor DNA in their bloodstream had genomic alterations that could hypothetically be targeted using existing FDA-approved drugs (as off-label use) or with therapies currently under investigation in clinical trials.

By definition, CUP does not have a definite anatomical diagnosis, but we believe genomics is the diagnosis, said Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health and senior author. Cancer is not simple and CUP makes finding the right therapy even more difficult. There are multiple genes and abnormalities involved in different areas of the body. Our research is the first to show that evaluating circulating tumor DNA from a tube of blood is possible in patients with CUP and that most patients harbor unique and targetable alterations.

A blood or liquid biopsy is a diagnostic tool based on the idea that critical genetic information about the state of disease can be found in blood or other fluids. One vial of blood could be used to detect the onset of disease, monitor its progression and measure its retreat less invasively than a tissue biopsy.

Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine.

Another advantage of the liquid biopsy is that the location of the cancer does not matter, said Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine and first author. With a blood sample, we can analyze the DNA of tumors throughout the body to find targetable alterations. With tissue biopsies, we can only see genomic changes that are in that one site and that may not be the same as what is in different sites not biopsied, such as the lung or bone.

Liquid biopsies are relatively simple to get and can be obtained regularly to monitor changes over time, as was the case with a 60-year-old woman with CUP. Her case, which was evaluated by Brian Leyland-Jones, MB, BS, PhD and study co-author with colleagues at Avera Cancer Institute, was described in the study to show the changes observed in ctDNA over the course of her treatment.

What we saw was that the patient was responding to treatment, but the cancer had emerging new mutations, said Kurzrock. Whats new here is that we can do the same evaluation through a blood test that we previously could only do with a tissue sample. You will see these changes with a simple blood test and it is easy to repeat blood tests, but hard to repeat tissue biopsies.

The study also reported the case of an 82-year-old man who was prescribed a checkpoint inhibitor immunotherapy as part of his treatment because of a mismatch repair gene anomaly that is typically observed in less than two percent of patients. He showed a partial response within eight weeks and blood biopsies showed the tumor DNA disappearing.

We can see that each patient has different mutations in their tumor DNA, which means that treatment plans cannot be a one-size-fits-all approach; a personalized approach is needed, said Kato.

Kurzrock is already using liquid biopsy technology in the Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT) clinical trial a project focusing on the outcome of patients who have genomic testing performed on their tumors and are treated with targeted therapy.

The authors suggest that a liquid biopsy approach should be further investigated in next-generation clinical trials focusing on CUP.

Co-authors include: Nithya Krishnamurthy, Scott M. Lippman, UC San Diego; Kimberly C. Banks, Richard B. Lanman, Guardant Health, Inc.; Pradip De, Kirstin Williams, and Casey Williams, Avera Cancer Institute.

This research was funded, in part, by the National Cancer Institute (P30 CA016672) and the Joan and Irwin Jacobs fund.

Disclosure: Razelle Kurzrock receives consultant fees from X-biotech and from Actuate Therapeutics, as well as research funds from Genentech, Pfizer, Sequenom, Guardant, Foundation Medicine and Merck Serono, and has an ownership interest in Novena Inc. and CureMatch Inc.

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Blood Biopsy Reveals Unique, Targetable Genetic Alterations in Patients with Rare Cancer – UC San Diego Health

Genetic drivers of deadly brain cancer uncovered – Medical News Today

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Genetic drivers of deadly brain cancer uncovered – Medical News Today

Blood biopsy helps identify targetable genetic alterations in patients with cancer of unknown primary – News-Medical.net

August 16, 2017

Using fragments of circulating tumor DNA in blood, University of California San Diego School of Medicine researchers were able to identify theoretically targetable genetic alterations in 66 percent of patients with cancer of unknown primary (CUP), a rare disease with seven to 12 cases per 100,000 people each year.

In order to plan treatment for cancer in general, physicians first attempt to pinpoint the primary cancer -; where the tumor first developed. In CUP, despite its spread throughout the body, the origin remains unknown, making treatment more difficult. The current standard of care is platinum-based combination chemotherapies with a median survival time of six to eight months.

In a study published in the journal Cancer Research on August 15, researchers report that by sequencing circulating tumor DNA (ctDNA) derived from blood samples in 442 patients with CUP, they were able to identify at least one genetic alteration linked to cancer in 290 -; 66 percent -; of patients. Researchers used a screening test developed by Guardant Health that evaluates up to 70 genes. Based on known carcinogenic mutations, 99.7 percent of the 290 patients who had detectable tumor DNA in their bloodstream had genomic alterations that could hypothetically be targeted using existing FDA-approved drugs (as off-label use) or with therapies currently under investigation in clinical trials.

“By definition, CUP does not have a definite anatomical diagnosis, but we believe genomics is the diagnosis,” said Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health and senior author. “Cancer is not simple and CUP makes finding the right therapy even more difficult. There are multiple genes and abnormalities involved in different areas of the body. Our research is the first to show that evaluating circulating tumor DNA from a tube of blood is possible in patients with CUP and that most patients harbor unique and targetable alterations.”

A blood or “liquid biopsy” is a diagnostic tool based on the idea that critical genetic information about the state of disease can be found in blood or other fluids. One vial of blood could be used to detect the onset of disease, monitor its progression and measure its retreat less invasively than a tissue biopsy.

“Another advantage of the liquid biopsy is that the location of the cancer does not matter,” said Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine and first author. “With a blood sample, we can analyze the DNA of tumors throughout the body to find targetable alterations. With tissue biopsies, we can only see genomic changes that are in that one site and that may not be the same as what is in different sites not biopsied, such as the lung or bone.”

Liquid biopsies are relatively simple to get and can be obtained regularly to monitor changes over time, as was the case with a 60-year-old woman with CUP. Her case, which was evaluated by Brian Leyland-Jones, MB, BS, PhD and study co-author with colleagues at Avera Cancer Institute, was described in the study to show the changes observed in ctDNA over the course of her treatment.

“What we saw was that the patient was responding to treatment, but the cancer had emerging new mutations,” said Kurzrock. “What’s new here is that we can do the same evaluation through a blood test that we previously could only do with a tissue sample. You will see these changes with a simple blood test and it is easy to repeat blood tests, but hard to repeat tissue biopsies.”

The study also reported the case of an 82-year-old man who was prescribed a checkpoint inhibitor immunotherapy as part of his treatment because of a mismatch repair gene anomaly that is typically observed in less than two percent of patients. He showed a partial response within eight weeks and blood biopsies showed the tumor DNA disappearing.

“We can see that each patient has different mutations in their tumor DNA, which means that treatment plans cannot be a one-size-fits-all approach; a personalized approach is needed,” said Kato.

Kurzrock is already using liquid biopsy technology in the Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT) clinical trial -; a project focusing on the outcome of patients who have genomic testing performed on their tumors and are treated with targeted therapy.

The authors suggest that a liquid biopsy approach should be further investigated in next-generation clinical trials focusing on CUP.

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Blood biopsy helps identify targetable genetic alterations in patients with cancer of unknown primary – News-Medical.net

What can genetic testing really tell you? – Popular Science

Once difficult and expensive even for the most technologically advanced labs, genetic testing is fast becoming a cheap and easy consumer product. With a little spit and 200 dollars, you can find out your risk for everything from cystic fibrosis to lactose intolerance.

But its important to remember that not all genetic tests are created equal. And even the best clinical genetic test, carried out in a medical lab under a doctor’s supervision, isn’t perfectgenes are important, but they don’t seal your fate.

Genetic tests are diagnostic, so anyone who is curious about their health can get one done. But they’re more informative if you think you might be at risk for a genetic disorder.

Heavy-duty genetic tests have been used as a clinical tool for almost half a centurylong before 23andMe and Ancestry.com began offering direct-to-consumer tests. Lets say that many women in your family have had breast cancer. You can get a genetic test to see if you may have inherited an abnormal version of the BRCA gene, known to increase your risk for breast cancer.

Heidi Rehm, associate professor of pathology at Harvard Medical School, is the director of the Laboratory for Molecular Medicine, where patients get tested for diseases that can be traced to specific genetic roots. She says it is most common for people to get tested when they either suspect or know that they have a genetic disease; it may have affected multiple people in their family or they could show symptoms of something widely known to be genetic, like sickle cell anemia. For these people, genetic tests can provide a much-needed explanation for an illness and help doctors determine the best course of treatment. Babies are often tested for genetic diseases, either while they are still fetuses or shortly after birth.

Others get genetic tests if they and their partner both have family histories of an inherited diseaseeven if they dont have the disease themselves. For example, cystic fibrosis is linked to one particular gene, but you have to inherit the abnormal version of the gene from both your parents to get the disease. If you only inherit one copy, you may never knowyou wont display any of the symptoms. But if you and your partner both carry one copy of the faulty gene, your child could still inherit two copies. Genetic tests can forewarn you of that possibility.

But Rehm says there has been a recent trend of healthy people getting tested to predict whether theyll get certain diseases. I do think there are settings where predictive genetic testing is incredibly important and useful, Rehm says; for example, knowing that youre at risk for breast cancer gives you the opportunity for early intervention (remember when Angelina Jolie got a double mastectomy upon finding out she had a mutated BRCA gene?)

But Rehm also points out that genetic tests may not be as straightforward as they seem. For example, some genes are thought to increase risk of getting a certain disease, but it might only happen if you have specific family history, or you might be able to reduce your risk with lifestyle changes. So remember that a genetic test isnt the final verdictthere are other factors at play too.

Not entirelyits scope is limited. For starters, not all diseases are caused by genes. Plenty of conditions stem from environmental and lifestyle factors; they may interact with your genes, but the external factors are the real trigger.

But even if a disease is caused solely by faulty instructions written in your genes, you wont necessarily be able to test for it. Thats because genetic tests are mainly used for diseases that are penetrant, a term that scientists use to describe a strong connection between having a certain gene (or multiple genes) and getting a disease.

Genetic tests are surprisingly simple on the surface. All thats required of you is a small sample of cells, like a blood sample or saliva (which doesnt have DNA itself, but picks up cheek cells during its journey out of your mouth). It get sent to a lab where sequencing machines match up small pieces of synthetic DNA with your DNA to figure out the overall sequence.

Once they have your sequence, geneticists can compare it with “normal” or disease-causing sequences. In the end, they might give you a yes or no answer, or sometimes youll get a probabilitya measure of how much your genes increase your risk of developing the disease. Then, its up to your doctor to figure out what these genes (in combination with your lifestyle, family history and other risk factors) mean for your health.

With penetrant diseases, theres a very, very high ability to explain the disease, Rehm says. For example, the breast cancer-related gene BRCA1 can give you a 60 percent chance of getting breast cancer (in Jolies case, with her family history, the risk was 87 percent.)

This makes genetic tests better at detecting so-called rare diseases, says Steven Schrodi, associate research scientist at the Marshfield Clinic Research Institutes Center for Human Genetics, but theyre less useful when it comes to more common diseases, like heart disease or diabetes. Genetics can increase your likelihood of getting these disease, but scientists still dont know quite how much. Part of the problem is that there may be dozens or hundreds of genes responsible for these diseases, Schrodi says.

We have an incomplete understanding of why people get diseases, Schrodi says. A large part of it hinges on how we define diseases. Perhaps physicians have inadvertently combined multiple diseases together into a single entity.

Consumer genetic teststhe ones where you send in samples from homesometimes claim to test for these more complex traits, but be careful: Their results might not be very medically relevant, Rehm says. If they tell you that your genes make you twice as likely to develop diabetes, for example, that’s a marginal increase that doesn’t significantly affect your risk, especially when you take into account lifestyle factors.

Genes do seem to play a role in determining lifespan. After all, some family reunions stretch from great-great-grandparents all the way down to infants. Scientists have studied centenarianspeople who lived to be 100 years oldand found that people with certain versions of genes involved in repairing DNA tend to live longer.

This makes sense because aging leaves its mark on your DNA. Environmental factors can damage DNA, and even the routine chore of replicating cells can introduce errors as the three billion units of your DNA are copied over and over. Long-lived individuals have different sequences that seem to make their cells better at keeping DNA in mint condition.

But figuring out your expiration date is more complex than just testing for a few genes, says Jan Vijg, professor of genetics at Albert Einstein College of Medicine. In theory, you could design a test that looks at specific genes that might measure your risk for developing Alzheimers Disease or other age-related diseases, or your risk for aging quickly. To some extent, yes: Biomarkers will tell you something about your chances of living a long life, Vijg says. Still, that will only work if you live a careful life. And that means no accidents, infections, or cancers.

Aging also affects the exposed ends of your DNA, called “telomeres.” DNA is stored as chromosomes, those X-like structures that you may have seen in biology textbooks. The most vulnerable parts of the chromosome are the chromosomes tips, which get shorter as you age because they arent properly replicated. But while telomere length might let you compare your DNA now with your DNA from a decade ago, you cant compare your own telomeres with other peoples telomeres. Theres a lot of variation between individuals, Vijg says. Some of us are just old souls (on the genomic level, that is.)

The methylation test, which looks at how the presence of small chemical groups attached to your DNA changes as you age, might be a better bet. A study at UCLA showed that changes were slower in longer-lived people. But Vijg is hesitant: I would not put my hopes on that as a marker to predict when exactly youre going to die.

For now, just enjoy your life, because you cant predict death. And if you decide to unlock the secrets of your DNA with an at-home test, don’t take those results for more than their worth.

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What can genetic testing really tell you? – Popular Science

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders – Medical Xpress

August 16, 2017 by Anna Williams Northwestern Medicine scientists used induced-human neurons (pictured here in green) derived from patient stem cells. The synaptic proteins, or connections, are marked in cyan and red. Credit: Northwestern University

Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and related disorders.

Peter Penzes, PhD, the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences, was a lead author of the study, published in the journal Cell Stem Cell. Marc Forrest, PhD, a post-doctoral fellow in Penzes’ laboratory, was the first author.

Over the last decade, large genetic studies have identified thousands of genetic variants associated with mental disorders. Most of these risk variants, however, are found within non-coding regionsparts of DNA that do not encode for proteinswhose function in disease development has been poorly understood.

“Ten years ago, there was very little known about the genetic basis of mental disorders like schizophrenia. Now the problem is the opposite: we have too many genes,” Penzes said. “Studying each variation one by oneand how it contributes to actual diseaseis difficult, so methods to reduce that number can be very useful. And that’s what this study did.”

The scientists demonstrated that by mapping out open chromatin regions in neurons derived from human stem cells, they could identify active non-coding DNA that contain a key subset of psychiatric risk variants that are most relevant to disease.

While the model was demonstrated in schizophrenia, the same method could be applied to other mental disorders as well, such as autism spectrum disorders or bipolar disorder.

Developing such a technique is critical to help scientists in the field concentrate their efforts on investigating the most important variants.

The findings also deepen the overall understanding of how such non-coding regions affect disease.

As a case study, the scientists used the new model to analyze thousands of risk variants that have been associated with schizophrenia and narrowed it down to a small list of key variants, of which they chose one to investigate.

They then used the gene-editing tool CRISPR to alter that risk variant into a variant not associated with disease, and demonstrated that the change had an effect on the connectivity of the cell, suggesting it played a role in neurodevelopment.

“In the past, these non-coding regions have been called ‘junk DNA’ because there was this misconception that they had no function,” Forrest said. “With this kind of technique, we’re starting to understand how non-coding regions can affect disease risk, even if they have more indirect roles than the actual protein-coding regions.”

In the future, the model using human neurons from induced stem cells could also serve as a valuable tool to screen potential drugs for such disorders, and discover which ones result in changes in the neuronal phenotype, Penzes said.

Explore further: Defect in non-coding DNA might trigger brain disorders such as severe language impairment

More information: Marc P. Forrest et al. Open Chromatin Profiling in hiPSC-Derived Neurons Prioritizes Functional Noncoding Psychiatric Risk Variants and Highlights Neurodevelopmental Loci, Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.07.008

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Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders – Medical Xpress

Sports medicine doctor on how to combat knee arthritis symptoms – CBS News

A new study found osteoarthritis of the knee is more than twice as common as it was just a few generations ago. It’s estimated that the lifetime risk of developing this condition is 46 percent.

However, it is possible to protect your knees and even reverse some of the symptoms. Dr. Jordan Metzl, a sports medicine physician at New York’s Hospital for Special Surgery, joined “CBS This Morning” to discuss what might be causing the increase and what you can do to reduce arthritic symptoms.

Asked what people are doing wrong when it comes to arthritis, Metzl said, “They’re not recognizing the symptoms of arthritis.”

The first thing to do if you are having symptoms, Metzl said, is to get an X-ray, which will show if there is a “narrowing between the bones.”

Metzl also credits the inactivity of modern life. “If you were alive 100 years ago, you walked more, you were much more active,” Metzl said.

“As this study shows us, the incidence of arthritis, the prevalence has more than doubled in the past hundred years and there are some different reasons for why that may be including people living longer and having higher weights but also related to activity,” Metzl said.

X-rays of what a healthy knee versus an arthritic knee looks like.

CBS News

To reduce symptoms, he says the best thing to do is strengthen your muscles with exercises like squats and lunges instead of saying off of the knee and, in effect, becoming more inactive.

“We want them to be very active. When they get arthritis I get them started on exercise, strengthening,” Metzl said.

While he says the wrong shoes can play a part in making symptoms worse, they don’t necessarily cause arthritis.

“I think the shoes may be part of making the symptoms worse. I don’t think it really has a lot to do with the reasons people get arthritis which are probably genetic, longevity, body index and then maybe inactivity but once you have arthritis we do a lot to control your symptoms,” Metzl said.

2017 CBS Interactive Inc. All Rights Reserved.

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Sports medicine doctor on how to combat knee arthritis symptoms – CBS News

Studying How Genes, Environment Contribute to Juvenile Arthritis – UB School of Medicine and Biomedical Sciences News

James N. Jarvis, MD, is conducting a study of the gene-environment paradigm for juvenile idiopathic arthritis pathogenesis.

Published August 14, 2017

James N. Jarvis, MD, clinical professor of pediatrics, will use an Arthritis Foundation grant to study how genes and environment work together to influence the immune dysfunction in juvenile arthritis.

After asthma, juvenile idiopathic arthritis (JIA) is the most common chronic disease condition in children. While genetics play a small role in the disease, environmental factors are also known to be important.

The study, titled Interplay Between Genetics and Epigenetics in Polyarticular JIA, builds upon previous work by Jarvis and his fellow researchers.

The epigenome refers to the features of DNA and the proteins that DNA is wrapped around that do not control the genetic makeup of a person but do influence how cells respond to the environment, says Jarvis, principal investigator on the grant.

Specifically, the epigenome determines what genes a cell will turn on or turn off in response to environmental cues, he notes.

Like most complex traits, genetic risk for JIA is principally located within non-coding regions of the genome.

Our preliminary studies present the hope that we can finally understand the gene-environment paradigm for JIA pathogenesis, Jarvis says.

Rather than regarding JIA as an autoimmune disease, triggered by inappropriate recognition of a self protein by the adaptive immune system, Jarvis hypothesizes that JIA emerges because leukocytes suffer genetically and epigenetically mediated perturbations that blunt their capacity to regulate and coordinate transcriptions across the genome.

This loss of coordinate regulation leads to inappropriate expression of inflammatory mediators in the absence of the normal external signals typically required to initiate or sustain an inflammatory response, he says.

Our field has been dominated by a single hypothesis for JIA pathogenesis for 30 years, Jarvis notes. However, as the field of functional genomics becomes increasingly wedded to the field of therapeutics, our work carries the promise of completely new approaches to therapy based on a completely different paradigm of pathogenesis.

The researchers are recruiting 30 children with newly diagnosed polyarticular JIA for its study to survey the epigenome and CD4+ T cells in them and compare the results with findings in 30 healthy children.

We plan to build a multidimensional genomic map that surveys the functional epigenome, examines underlying genetic variation and examines the effects of genetic and epigenetic variation on gene expression, Jarvis says.

He notes the work will focus on CD4+ T cells because the researchers have already identified interesting interactions between their epigenome and transcriptome in the context of therapeutic response in JIA.

Because the epigenome is the medium through which the environment exerts its effects on cells, Jarvis believes that characterizing the epigenome in pathologically relevant cells, ascertaining where epigenetic change is linked to genetic variation and determining how genetic and epigenetic features of the genome regulate or alter transcription is the key to truly understanding this disease.

This project addresses a question that parents always ask, which I never thought wed begin to answer in my lifetime: What causes JIA? This study wont provide the whole answer, but it will go a long way toward taking us there, he says.

The project has three specific aims:

The two-year, $730,998 grant is part of the Arthritis Foundations 2016 Delivering on Discovery awards. It was one of only six projects out of 159 proposals chosen for funding. For the first time, arthritis patients helped the foundation select projects.

Including patient input as part of the selection process was a new milestone in patient engagement for the Arthritis Foundation and allowed us to select projects that hold the most promise from an arthritis patients point of view, says Guy Eakin, senior vice president, scientific strategy.

Collaborators from the Jacobs School of Medicine and Biomedical Sciences are:

Other collaborators include researchers from the Childrens Hospital of Philadelphia.

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Studying How Genes, Environment Contribute to Juvenile Arthritis – UB School of Medicine and Biomedical Sciences News

First human embryo genetically modified in the US – Dailyuw

Researchers from Portland, Ore. genetically modified human embryos for the first time on American soil, but this is not a new feat. The process has already been done in China. To date, no genetically modified embryo has been inserted into a womb.

The lead researcher, Shoukhrat Mitalipov of Oregon Health and Science University, has a history of embryo work and demonstrated this round that its possible to safely remove inherited diseases by changing defective genes. This is called germline engineering. However, none of the embryos were allowed to last longer than a few days and the results are still pending publication.

Germline engineering typically uses CRISPR-Cas9, technology which precisely alters DNA. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.

At its roots, CRISPR is comprised of a small piece of RNA and a protein called Cas9. The RNA is preprogrammed to match a specific genetic code to then subsequently alter a specific strand of DNA once injected. The RNA guides the injection, and Cas9 tags along because, as an enzyme, it is able to break the DNA at an exact spot.

The challenge is that DNA tends to repair itself pretty fast. To avoid this, some CRISPR injections carry another strand of DNA the cell can use to fix the break thats created, therefore allowing genetic alterations.

The implications are very large, Dr. Charles Murry, Director of the UW Medicines Institute for Stem Cell and Regenerative Medicine, said. It gives us the ability to permanently eradicate a genetic disease from a familys pedigree. And as a physician, thats something thats extremely exciting to me.

Genetic modifications have been around for decades, and CRISPR has applied since early 2013. The possibilities for CRISPR were first realized through a natural bacterial process that defends against invasive viruses also known as this all started with yogurt, surprise.

However, the real breakthrough happened in 2015 with Junjiu Huangs first human embryo edits in China. Scientists are also looking at this system to eliminate pests and the diseases they carry.

Theres another side to it of course, Murry contended. When humans begin to rewrite our own genetic code, and there are all kinds of chances to not only make corrections as we edit but to make new mistakes as we edit we may inadvertently create problems in the attempt to solve others.

UW Health Sciences and Medicine public information editor Leila Gray said UW Medicine researchers are using CRISPR on specific somatic cells, which are the ones that make up your body. These cells were collected from patients with their approval. One team, for example, is trying to edit cells with kidney disease, studying certain conditions in petri dishes. But no UW researcher is reporting work to remove genetic diseases from human embryos.

Currently, the National Institutes of Health wont federally fund this research. However, the National Academy of Sciences and the National Academy of Medicine are recommending cautious reconsideration.

Murry predicts that before any of this would apply to a human being, a large animal would have to successfully carry to term a genetically modified embryo. Scientists would also likely have to monitor the newborns life afterward.

There are ethical conundrums with this new technology. Its so concerning that upon its first big embryonic debut, there was a three-day summit in December 2015 for hundreds of local and global scientists, policymakers, and the US presidential science adviser.

Some worry genetic engineering could lead to a dark future where humans are pre-edited for appearance, physical strength, or intelligence.

George Church, a Harvard Medical School geneticist, first told the Washington Post two years ago that there were nearly 2,000 genetic therapy trials already underway that didnt use CRISPR. The difference between those and the few that have is cost.

Its about 1,000 times cheaper for an ordinary academic to do, Church is quoted in the article. It could be a game-changer.

Reach reporter Kelsey Hamlin at news@dailyuw.com. Twitter: @ItsKelseyHamlin

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First human embryo genetically modified in the US – Dailyuw

Researchers find genetic precursors of leukemia in patients treated for non-blood cancers – Medical Xpress

August 14, 2017 Catherine Coombs, MD, is an associate member at UNC Lineberger and assistant professor in the UNC School of Medicine.

In a study of nearly 9,000 people treated for solid tumor cancers, researchers found that radiation treatment and tobacco use were linked to higher rates of blood-based DNA mutations that could lead to higher risk for blood cancers like leukemia.

The study, published in the journal Cell Stem Cell, revealed new risk factors for “clonal hematopoiesis,” a medical phenomenon in which genetic mutations are found in the blood cells of patients who do not have an existing blood cancer. Twenty-five percent of the patients in the study had clonal hematopoiesis. Of the subset of patients they actively followed, those with clonal hematopoiesis had a small 1 percent but increased, estimated incidence of developing blood cancer later on.

“The presence of clonal hematopoiesis can lead to an increased risk for subsequent blood cancers,” said UNC Lineberger’s Catherine Coombs, MD. “We wouldn’t recommend forgoing treatment that is medically indicated because the risk of a secondary cancer is relatively low, but it is important to closely watch those patients who are high-risk.”

Coombs was first author of the study at the Memorial Sloan Kettering Cancer Center in New York, where she completed a fellowship in oncology before coming to UNC Lineberger. The study analyzed genetic changes from 8,810 MSK cancer patients. The researchers found clonal hematopoiesis in 25 percent of patients, with the highest incidence in patients with thyroid cancer, and the lowest in patients with germ cell tumors. Mutations were more common in older people, with the odds of clonal hematopoiesis increasing 6 percent for each decade above age 30. Clonal hematopoiesis was also strongly associated with current or former tobacco use.

“A major risk factor for developing clonal hematopoiesis that can be modified or changed is tobacco use,” Coombs said.

They also found a higher frequency of patients with clonal hematopoiesis who had received radiation therapy. Forty-one percent of patients with clonal hematopoiesis received radiation, compared to 35 percent of patients who did not have clonal hematopoiesis, and had received radiation.

Risk for developing a secondary blood cancer was very small in the patient population overall. Only 19 out of the 5,394 patients the researchers actively followed developed a new blood cancer within 18 months. However, for patients who did get a blood cancer, the risk was higher for patients who had clonal hematopoiesis. One percent of patients with clonal hematopoiesis were estimated to develop a secondary cancer, which was three times higher than the estimated 0.3 percent for patients who developed blood cancer and did not have clonal hematopoiesis.

“This has been borne out by other groups: if you have these clonal hematopoiesis mutations, you have a greater risk for developing hematologic cancer than do patients who don’t have them,” she said.

Coombs said more research is needed to determine the cause of these increases.

Explore further: Biomarker may predict which formerly treated cancer patients will develop highly fatal form of leukemia

More information: Catherine C. Coombs et al. Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes, Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.07.010

How do initially benign forms of cancer evolve to become aggressive? In a quest to answer this long-standing question, an EU project has studied the growth and clonal evolution of chronic lymphocytic leukaemia (CLL)a blood …

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Researchers find genetic precursors of leukemia in patients treated for non-blood cancers – Medical Xpress

Family with Cancer Syndrome Finds Hope at University of Arkansas for Medical Sciences – KATV

Melinda Godsey was enjoying a normal day visiting her family in Little Rock when she started to feel sick. I thought I had a stomach virus, she said. Not wanting to infect her grandchildren, she got up the next morning and started the drive back to her home in El Dorado.

Feeling weaker and weaker as the two-hour trip progressed, Godsey, an interior designer and artist, recalls the frightening moment when she passed out behind the wheel. It was quick. I just faded in and out. Thankfully I didnt cross any lanes of traffic, she said.

Her weakness continued to progress over the next three days, getting to the point where she could not shower or speak. After being admitted to the hospital, doctors found what looked to be the cause of her weakness: Severe bleeding ulcers in her stomach had resulted in a significant loss of blood.

However, that wasnt the only thing they found. Tests also revealed that the ulcers were merely a symptom of a much larger problem that had likely been growing for months. Godsey was living with linitis plastica, a rare stomach cancer that spreads to the muscles of the stomach wall, causing it to harden and become rigid. While this aggressive cancer starts in the stomach, it quickly spreads to other organs, making treatment options limited and complex.

While this diagnosis was about to change Godseys life, she did not yet know the impact it would have on her loved ones as well.

Linitis plastic represents from 5 percent to 10 percent of all gastric cancers, and a slight increase in cases has been observed over the past few years. This may be attributed to improved diagnostic tools, says Luidmila Schafer, M.D., a medical oncologist and assistant professor in the UAMS College of Medicine Department of Internal Medicine.

Our knowledge and ability to diagnose rare cancers has improved significantly in recent years, so conditions such as linitis plastica may not have been diagnosed with such precision in the past, she explains.

Godsey was referred by her physician in El Dorado to a cancer center out of state, where she immediately went for evaluation. After confirming her diagnosis, she was given the news that the cancer had already spread to her abdomen and the preferred surgical treatment was no longer an option. However, she was a candidate for aggressive chemotherapy.

Because her out-of-state physician received his fellowship training in the UAMS Hematology/Oncology Fellowship program, he was aware of the UAMS Winthrop P. Rockefeller Cancer Institute and its comprehensive treatment programs. He told Godsey that she could return to Arkansas and receive chemo at the Cancer Institute close to home.

Referrals were made and Godsey arrived for her first appointment at UAMS in June, about one month after her diagnosis. Unfortunately, good news did not await her. Godsey had developed sepsis as the result of an infection, resulting in a week-long hospitalization and postponement of the start of chemotherapy.

It was a tough start, said Godseys daughter, Courtney Cassinelli, adding that after the infection cleared, her mom was able to begin two types of chemo given simultaneously under Schafers supervision.

While the treatment has been tough, Godsey is thankful for her good days and the time shes been given.

I could have lived for only a short time, but Ive made it two years thanks to Dr. Schafers care. What she has done for me has been remarkable, she said.

A Family Connection

At about the same time that Godsey was coming to terms with her diagnosis of stage 4 stomach cancer in 2015, her first cousin, Anita Meek, was getting the news that she had been diagnosed with lobular breast cancer. This form of breast cancer makes up only about 10 percent of invasive breast cancers and typically doesnt form a lump, making it less likely to be detected on a mammogram.

Having lost a young son to cancer, Meek, who lives in Harrison, decided to undergo genetic testing to see if there might be an inherited genetic component to their conditions. Schafer also recommended that Godsey undergo genetic testing at the UAMS Cancer Genetics Clinic due to the rarity of her cancer and the known link between linitis plastica and the CDH1 gene mutation.

As the only cancer genetics clinic in Arkansas, we see people with rare cancers, early-onset cancers or unusual presentations of cancer from across the state and region, said Kent McKelvey, M.D., director of Cancer and Adult Genetic Services and associate professor of family medicine and genetics in the UAMS College of Medicine.

UAMS has the only board-certified geneticists who diagnose, manage and treat complex cancer syndromes, of which there are more than 50. Cancer genetics counselors work with the geneticist and are a vital part of the team to help families understand their genome and its implications in cancer prevention.

Although any doctor can order genetic testing which is conducted using a blood or saliva sample the process can be daunting. Abnormal results must be put into context for a specific patient and family in this rapidly changing field and no two cases are the same.

When both Godsey and Meek were found to have the CDH1 gene mutation it only took minutes for McKelvey to conclude it was passed to them by their fathers, who were brothers.

A person doesnt inherit cancer from their parents. However, they can inherit the predisposition to cancer. Thats what happened in this family. The CDH1 gene mutation that Mrs. Godsey and Mrs. Meek have increases their risk of developing linitis plastica by about 80 percent and lobular breast cancer by about 40 percent, McKelvey said.

There also is, to a lesser extent, an increased risk of colon cancer associated with CDH1.

Moving Forward

Armed with this information, Meek underwent a double mastectomy at a hospital near her Northwest Arkansas home and continues to be followed twice yearly at Highlands Oncology Group (HOG). The UAMS Cancer Institute and HOG formed a partnership in 2013 that provides expanded access to clinical trials and advanced treatment options to residents of Northwest Arkansas.

Because Godsey and Meek now knew they carried the CDH1 mutation, they also knew their adult children could choose to undergo genetic testing to determine if they had inherited it as well. When someone carries a gene mutation, they have a 50-50 chance of passing that mutation along to each of their children.

My sister and I were both tested at UAMS. My test came back negative, but hers was positive, said Cassinelli. Because Cassinelli does not carry the gene mutation, there is no need to test her children. Once the line is broken, it does not reappear in subsequent generations.

As for Kelly Cameron, Godseys eldest daughter, the positive result set in motion a series of completely unexpected and life-changing decisions.

Because there is no screening method for stomach cancer, it is often found in its late stages after it has already spread to other organs, which was the case with Godsey. The only way to prevent a person with the CDH1 gene mutation from developing stomach cancer is to undergo a procedure called total gastrectomy, which involves removing the stomach and extending the small intestine up to meet the esophagus. With time, the small intestine makes a small pouch mimicking the stomach.

Because food now passes directly into the small intestine when it is consumed, side effects such as bloating, nausea, vomiting, cramps and diarrhea following total gastrectomy are common in the first few months.

Although it is possible to adjust to the new diet and small meals required following total gastrectomy, the surgery also has an impact on a persons physical, social and emotional health, Schafer said.

Due to her young age and the high likelihood that she would develop this rare cancer in her lifetime, the 41-year-old Cameron decided that, regardless of the side effects, total gastrectomy was her best option.

While it has been a challenging transition since her surgery in February 2016, each month becomes a little bit easier for Cameron. The first year is traumatic to your body. Your stomach is a major player and suddenly its gone. You cant fully understand what thats like unless you experience it yourself, she said.

Ultimately, however, the body adapts to its new situation and the symptoms subside. Its a new normal, Cameron said, adding that she has essentially relearned how and what to eat, in addition to taking vitamin supplements that ensure she meets her daily nutritional needs.

Although Meek also is at risk of developing linitis plastica, she elected to forego total gastrectomy for now. If I were younger, I may have chosen that path as well. Instead, Im seeing my doctor regularly and hoping that any signs of cancer will be found early, she said.

Additional Prevention

While still adjusting to her total gastrectomy, Cameron also decided in December 2016 to undergo a bilateral prophylactic mastectomy by having both breasts removed before there was any evidence of cancer.

According to the National Cancer Institute, this surgery will reduce her risk of developing breast cancer by at least 95 percent. The surgery was performed in December 2016 by V. Suzanne Klimberg, M.D., who was then director of the UAMS Breast Cancer Program.

She will soon finish the breast reconstruction process led by plastic surgeon Eric Wright, M.D., associate professor in the UAMS College of Medicine Division of Plastic and Reconstructive Surgery.

Cameron is thankful the surgical options were presented to her by McKelvey after completing her genetic test.

He was a straight shooter. He told me exactly what I needed to do if I wanted to eliminate the chance of developing these cancers, she said.

She also is thankful to have gone ahead with the surgeries at a young age, as the total gastrectomy revealed stage 1 cancer already formed in the lining of her stomach, as well as precancerous cells in one breast.

If not for that genetic test and Dr. McKelveys guidance, I would have had a much earlier onset of disease than my mom did. Knowing my genetic makeup saved my life, she said.

Next Steps

Now that her surgeries are complete, next on Camerons list is yearly colonoscopies at UAMS to screen for early signs of colon cancer. Thankfully there is a successful screening method for colon cancer, so no preventative surgery is needed there, she said.

Then, after her son turns 18, he will have the opportunity to undergo genetic testing at UAMS for the CDH1 gene mutation and make his own decisions based on those findings. Some of Godseys siblings and other relatives also have agreed to undergo testing to see if they carry the gene and may have passed it to their children.

In addition to providing individuals with knowledge about their personal health risks, genetic tests also assist researchers in better understanding cancer syndromes in the future.

Our ability to diagnose and understand cancer and other genetic syndromes is changing on a weekly basis. Because of this, we need the ability to bank and store individual genomes and tumor samples that can be compared and analyzed for a better understanding of how these syndromes work. As more samples are documented, our knowledge will continue to grow, says McKelvey.

Godsey and Cameron agree they found the right place to address their complex medical needs.

The Cancer Institute at UAMS has been wonderful. Theyve treated me not only like a patient, but more like a friend. Members of the staff have even called to check on me at home. I would never go anywhere but UAMS, Cameron said.

The University of Arkansas for Medical Sciences is the home of our states only academic health sciences center. With clinics covering nearly every medical specialty, our research and educational programs inspire new knowledge that results in better diagnosis and more advanced patient care. To learn more about UAMS or schedule an appointment with one of our physicians, visit uamshealth.com.

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Family with Cancer Syndrome Finds Hope at University of Arkansas for Medical Sciences – KATV

Editorial: The growth of regenerative medicine – Concord Monitor

The field is called regenerative medicine, technology that shows promise of repairing or replacing human organs with new ones, healing injuries without surgery and, someday, replacing cartilage lost to osteoarthritis.

New Hampshire could become one of the centers of the new industry and become the next Silicon Valley, says Manchester inventor Dean Kamen. The governor and Legislature, however, arent doing what they need to make the potential economic and intellectual boom more likely.

Sever the spinal chord of a zebra fish, an aquarium standby, and it will regrow in a couple of weeks. Remove a limb from a salamander, and it will grow another one indistinguishable from the first. And even some humans, especially when young, can regrow a new fingertip and fingernail on a digit severed above its last joint. Medical science is moving ever closer to performing such wonders.

3-D bioprinters that use biologic materials instead of printer ink are already printing replacement human skin. A University of Connecticut scientist and surgeon believes it will be possible to regenerate human knees sometime in the next decade and regrow human limbs by 2030.

At Ohio State University, a team has succeeded in using genetic material contained in a tiny microchip attached to skin and, with a tiny, Frankenstein-like zap of electricity, reprogram skin cells to produce other types of human cells. Turn a skin cell into say, a vascular system cell, and it will migrate to the site of a wound, spur healing and restore blood flow. Convert skin cells to brain cells and, with a few more steps, it could help stroke victims recover. The technologys potential is enormous.

Kamen created the portable insulin pump, and he and his team at DEKA Research in Manchesters millyard produced the Segway human transporter, a device that provides clean water in places that lack it, an external combustion engine that will soon heat and power part of the states mental hospital, and other inventions. Their track record helped Kamen and DEKA beat out plenty of other applicants to win $80 million in federal funds to found ARMI, the Advanced Regenerative Manufacturing Institute in Manchester. Total funding is now just shy of $300 million.

The governments aim is to spur technologies that could be used to treat injured soldiers but whats learned could aid everyone and make New Hampshire a mecca for scientists, production facilities, pharmaceutical companies and more. DEKA will not create the new technologies but use its inventing and engineering expertise to help companies scale up and speed up regenerative medicine technologies so they can be brought to the market more quickly at an affordable cost.

The states university system has partnered with DEKA to train students who will one day work in the biotech field. The educational infrastructure is in place, but its handicapped by the states sorry funding of higher education. New Hampshire regularly ranks last or next to last in state support and its students carry the most debt of any in the nation.

To make New Hampshire the biotech mecca Kamen envisions will require lawmakers to better fund higher education, support the regenerative manufacturing institute and make housing available. A high-tech company that wants to come to New Hampshire cant do so if its workers cant afford a home.

Regenerative medicine is expected to become a massive economic engine, one that will create jobs and improve lives while lowering health care costs. The Legislature should be doing all it can to make sure that at least some of that engine is designed and made in New Hampshire.

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Editorial: The growth of regenerative medicine – Concord Monitor

Career Opportunity Explosion in Genetics – PA home page

FORTY FORT, LUZERNE COUNTY (WBRE/WYOU) — In a time when many wonder about career opportunities of the future, there is one that’s showing signs of significant growth. It has to do with helping patients understand and address personal health risk factors.

The U.S. Bureau of Labor Statistics reports nearly 40,000 jobs were created last month in the health sector. Of that sector, one particular field is showing tremendous employment opportunity more than any other job.

What you’re witnessing is the future of medicine: unlocking genetic code secrets to personalize treatment and even prevention of certain illnesses and conditions. Both in and out of these DNA labs are genetic counselors who gather and analyze family history and inheritance patterns to help identify individuals and families who may be at risk. “It’s so such on the cutting edge of science and technology that it’s continuously changing and there are always new things to really keep on top of and excite me,” said Geisinger Genomic Medicine Institute Genetic Counselor Marci Schwartz.

Ms. Schwartz works in both cardiovascular and cancer genetics. By the end of 2024, the demand for genetic counselors like her is expected to grow by nearly 30 percent which is greater than any other job sector in the nation. So what’s driving that demand? “We are now getting to the point where genetic information is really becoming relevant to clinical care,” said Geisinger Genomic Medicine Institute Director Marc Williams, MD.

That care also includes targeted medicine in neurology, pediatrics, and prenatal genetics. Home to the 11 years and counting genome project “MyCode”, Geisinger anticipates needing hundreds of genetic counselors in the next few years. “We have a huge opportunity but also this deficit in terms of training personnel,” said Dr. Williams. Part of the genetic field job explosion is a recently created position by Geisinger called a genetic counseling assistant.

Geisinger Commonwealth School of Medicine in Scranton will soon offer a masters program in genomics but exploring career possibilities in this field can begin much sooner. “Some of the shadowing and volunteer experience can certainly be started in high school,” said Ms. Schwartz.

You don’t need to be a doctor to become a genetic counselor but you do need a masters degree. The starting salary for this growing profession is roughly $65,000 a year. You can learn more about career opportunities in genetic counseling by clicking here.

Originally posted here:

Career Opportunity Explosion in Genetics – PA home page

Human Germline Genome Editing Genetics bodies weigh in on debate with position paper – JD Supra (press release)

In an article published in American Journal of Human Genetics on 3 August 2017, an international group of 11 organisations with genetics expertise has issued a joint position statement, setting out 3 key positions on the question of human germline genome editing:

(1)At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

(2)Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

(3)Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

This serendipitously timed statement comes on the heels of Shoukhrat Mitalipov and colleagues at Oregon Health and Science Universitys publication of an article in Nature reporting the successful use of CRISPR/Cas9 in human embryos to correct a mutation in a gene called MYBPC3 that causes a potentially fatal heart condition known as hypertrophic cardiomyopathy. The publication of this article has drawn the attention of the wider mainstream media and reignited the public debate as to the desirability, feasibility and ethics of editing the human genome in an inheritable way.

Gene editing – putting the paper in context

Whilst debates about the ethics of gene editing (both somatic and germline) go back decades, human germline genome editing has never before been realistically possible from a technical standpoint. That has changed with the advent of the CRISPR/Cas9 system, whose efficiency and ease of use has not only opened up the field of gene editing to a far larger number of companies and laboratories than previously, but has brought the editing of specific genes in a human embryo out of the realms of fantasy into reality. The potential for such technology to improve quality of life and prevent suffering caused by debilitating genetically inherited diseases has captured the imagination of many, particularly people living with currently intractable genetic conditions, their friends and family. However, the power of the technology has also conjured up the familiar spectres of playing God, the uncertainty of long term effects on individuals (and what it means to be human itself), marginalisation of the disabled or genetically inferior and the potential for inequality to manifest itself genetically as well as socioeconomically.

Germline cell editing poses significantly more concerning ethical and regulatory issues than somatic cell editing. The latter will only result in uninheritable changes to the genome of a population of cells in the particular individual treated, whilst the former involves genetic changes that will be passed down, for better or worse, to the individuals offspring.

In early 2015, the first study demonstrating that CRISPR/Cas9 could be used to modify genes in early-stage human embryos was published. Although the embryos employed for those experiments were not capable of developing to term, the work clearly demonstrated that genome editing with CRISPR/Cas9 in human embryos can readily be performed. That report stimulated many scientists and organisations to clarify their stance on the use of genome-editing methods. The United Kingdom and Sweden have both approved experiments for editing DNA of a human embryo but not those that involve implanting embryos. In the UK, Human Fertilisation and Embryology Authority (HFEA) has approved an application by developmental biologist Kathy Niakan, at the Francis Crick Institute in London, to use CRISPR/Cas9 in healthy human embryos. Currently, such experiments cannot be done with federal funding in the United States given a congressional prohibition on using taxpayer funds for research that destroys human embryos. Congress has also banned the U.S. Food and Drug Administration from considering a clinical trial of embryo editing. As would be expected, the safety requirements for any human clinical genome-editing application are extremely stringent.

However, earlier this year, US-based National Academy of Sciences (NAS) and the National Academy of Medicine (NAM), published a report that concluded using genome-editing technology, such as CRISPR/Cas9, to make alterations to the germline would be acceptable if the intention was to treat or prevent serious genetic disease or disorders, and the procedure was proven to be safe ( significant and, to an extent, subjective hurdles to be overcome).

The ASHG position paper

The position paper was the product of a working group established by the American Society of Human Genetics (ASHG), including representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counsellors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counsellors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The group, composed of a combination of research and clinical scientists, bioethicists, health services researchers, lawyers and genetic counsellors, worked together to integrate the scientific status of and socio-ethical views towards human germline genome editing.

As part of this process, the working group reviewed and summarised nine existing policy statements on gene editing and embryo research and interventions from national and international bodies, including The International Society for Stem Cell Research (2015) Statement on Human Germline Genome Modification, The Hinxton Group (2015) Statement on Genome Editing Technologies and the statement released following the International Summit on Human Gene Editing (2015) co-hosted by the National Academy of Sciences, National Academy of Medicine, Chinese Academy of Sciences and The Royal Society (UK). It was observed that differences in these policies include the very definition of what constitutes a human embryo or a reproductive cell, the nature of the policy tool adopted to promote the positions outlined, and the oversight/enforcement mechanisms for the policy. However, by and large, the majority of available statements and recommendations restrict applications from attempting to initiate a pregnancy with an embryo or reproductive cell whose germline has been altered. At the same time, many advocate for the continuation of basic research (and even preclinical research in some cases) in the area. One notable exception is the US National Institutes of Health, which refuses to fund the use of any gene-editing technologies in human embryos. Accordingly, due to the lack of public funding in the US, work such as that done by Mitalipovs group must be privately funded.

The working group considered that ethical issues around germline genome editing largely fall into two broad categories those arising from its potential failure and those arising from its success. Failure exposes individuals to a variety of health consequences, both known and unknown, while success could lead to societal concerns about eugenics, social justice and equal access to medical technologies.

The 11 organisations acknowledged numerous ethical issues arising from human germline genome editing, including:

exposing individuals to potentially harmful health consequences, since the magnitude of the potential risks of off-target or unintended consequences are yet to be determined;

the risk that if highly restrictive policies are placed on the conduct and public funding of basic research in the field, this could push research out of the public eye and public interest, underground to private funders or overseas, to organisations and territories where it would be subject to less regulation, transparency and oversight. This could result in research not being subject to ethical and peer oversight, such as ethics board approval, data sharing, peer review and dissemination of research resources;1

the de facto inability of future individuals who are the result of genetic editing, to consent to that editing;

concerns around the boundaries of eugenic use of gene editing technology, which the groups acknowledged could be used to reinforce prejudice and narrow definitions of normalcy in our societies; and

ensuring the gene editing technologies do not worsen existing or create new inequalities within and between societies, noting: Unequal access and cultural differences affecting uptake could create large differences in the relative incidence of a given condition by region, ethnic group, or socioeconomic status. Genetic disease, once a universal common denominator, could instead become an artifact of class, geographic location, and culture. A dangerous consequence of such inequality could be that reduced incidence and reduced sense of shared risk could affect the resources available to individuals and families dealing with genetic conditions.

Having touched on each of these issues, the group then outlined its consensus positions:

1. At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

It was noted that there is not yet a high quality evidence base to support the use of germline genome editing, with unknown risk of health consequences and ethical issues still to be explored and resolved by society.

The group observed that two major categories of safety concerns are (i) the effect of unwanted or off-target mutations, and (ii) the potential unintended effects of the desired on-target base changes (edits) being made. It noted that it is reasonable to presume that any human genome-editing therapeutic application will require stringent monitoring of off-target mutation rates, but there remains no consensus on which methods would be optimal for this, or what a desirable maximum off-target mutation rate would be when these techniques are translated clinically. The working-group thus outlined its views on the minimum necessary developments that would be required (at least from a safety perspective) before germline genome editing could be used clinically:

definitions of broadly acceptable methodologies and minimum standards for measuring off-target mutagenesis;

consensus regarding the likely impact of, and maximum acceptable thresholds for, off-target mutations; and

consensus regarding the types of acceptable genome edits with regard to their potential for unintended consequences.

2. Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

The group agreed that conducting basic scientific [techniques?] involving editing of human embryos and gametes can be performed ethically via compliance with applicable laws and policies, and that any study involving in vitro genome editing on human embryos and gametes should be conducted under rigorous and independent governance mechanisms, including approval by ethics review boards and meeting any other policy or regulatory requirements. Public funding for such research was seen as important in ensuring that such research is not driven overseas or underground, where it would be subject to less regulation, oversight and transparency.

3. Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

Even if the technical data from preclinical research reaches a stage where it supports clinical translation of human germline genome editing, the working group stresses that many more things need to happen before translational research in human germline genome editing is considered. The criteria identified by the group in this position cut across medical, ethical, economic and public participation issues and represent the setting of an appropriately high and comprehensive standard to be met before human germline genome editing may be applied clinically. The group acknowledges the challenges of public engagement with such technical subject matter but encourages new approaches to public engagement and engagement of broader stakeholder groups in the public discussion.

The ethical implications of altering the human germline has been the subject of intense discussion in recent years, with calls for such work to be put on hold until the process of genome editing is better understood. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time.

The working group concludes that Many scientific, medical, and ethical questions remain around the potential for human germline genome editing. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time. We encourage ethical and social consideration in tandem with basic science research in the upcoming years.

This appears a reasonable position largely in line with the recommendations from the major national and international groups surveyed by the working group. It balances the need to encourage further basic research and validation with strong awareness of the ethical and societal implications of human germline genome editing, setting a high bar before such technology should be translated to the clinic. No doubt, however, the debate will continue, particularly in respect of public funding for such work. Whether the US will maintain their stance against public funding, in the face of international competition, and potential loss of talent and investment, remains to be seen.

Footnotes

1. In this connection it should be noted that China is a good example of a jurisdiction where there is very strong government investment in biotech, including CRISPR, and less regulatory standards than in the West. This combination of factors seems to be fuelling the pace of research there (many CRISPR firsts have come in China e.g. first CRISPR clinical trial in humans; first CRISPR editing of human embryos), but potentially at the risk of less rigorous, well controlled science being conducted (e.g. the recent retraction of the NgAgo paper).

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Human Germline Genome Editing Genetics bodies weigh in on debate with position paper – JD Supra (press release)

Medical marijuana’s legal, but schools fear crackdown if students use it – Sun Sentinel

School districts are in a quandary over students who use medical marijuana, with some fearing that any help they offer could land them in jail.

Voters in November agreed to legalize pot for medical purposes but its also a popular recreational drug considered illegal by the federal government. And that has raised a number of questions as districts scramble to put policies in place. Among them:

— Will local schools store the the drug on school premises or will parents have to come on campus to give it to their child?

— What forms of the drug will be acceptable on campus? Can students apply cannabis ointments or patches on their skin or bring edible brownies in their lunchboxes?

— What steps will schools take to prevent the drug from getting into the hands of other students?

Palm Beach County Schools Superintendent Robert Avossa said he plans to talk to School Board members to get a sense of what would best serve community.

We want to show compassion and also use common sense, he said. We may have to deal with it on a case-by-case basis.

Broward County school officials say they are awaiting guidance from the state Department of Education.

However, Lisa Maxwell, who heads the Broward County Principals and Assistants Association, said her group would fight any attempts to make administrators responsible for dispensing or storing the drugs. She said the federal government may disagree with the states decisions to allow minors to access the drugs, and that would put her members in legal peril.

We would vehemently oppose anyone being required to administer something that they could ultimately be criminally prosecuted for doing, she said.

School districts could potentially lose federal funding for school lunches and Title 1 programs for low-income students since the policies run afoul of federal government drug-free workforce policies, warned the Education Commission of the States, which studies education policy.

The expansion of marijuana use policies in the states has largely gone unchecked by federal officials; however, the expansion into schools presents a different set of issues and could meet some federal pushback, the commission wrote in a recent policy paper.

Seth Hyman of Weston is pushing Broward to move ahead on the issue.

His 11-year-old daughter, Rebecca, has a condition that requires her to use a wheelchair and a feeding tube. She also is prone to epileptic seizures.

Taimy Alvarez / Sun Sentinel

Seth Hyman plays with his daughter, Rebecca, 11, has 1P36 Deletion Syndrome, a genetic disorder, who benefits from medical marijuana in their Weston home.

Seth Hyman plays with his daughter, Rebecca, 11, has 1P36 Deletion Syndrome, a genetic disorder, who benefits from medical marijuana in their Weston home. (Taimy Alvarez / Sun Sentinel)

She takes medical marijuana orally three to four times a day, but she cant take it at her school, Manatee Bay Elementary, because the school doesnt have a policy that covered it.

I would like my daughter to have the option to get her medication however the law allows, he said.

Hyman believes school districts are protected due to the state law.

He works for Kelley Kronenberg, a Fort Lauderdale law firm, advising employers on how to comply with the law. He points to a 2013 memo by the U.S. Justice Department saying it was not a priority to enforce federal drug laws for people possessing marijuana for medical purposes. While the memo was from the Obama administration, Hyman said President Trump hasnt seemed concerned about medical marijuana.

Still, he admits there are no guarantees his administration wont try to ban it in schools,

But if that does come to fruition, there will probably be thousands of parents with medically complex kids kicking and screaming asking why they are being denied medicine that has not been proven to kill anyone, Hyman said. People have a right to some sort of improvement in their medical condition.

stravis@sunsentinel.com, 561-243-6637 or Twitter @smtravis

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Medical marijuana’s legal, but schools fear crackdown if students use it – Sun Sentinel

Making Sense of Medicine: Is your cellphone killing you? – The Daily News of Newburyport

Some are saying that Sen. John McCains brain cancer, glioblastoma, was the result of long-term cellphone usage. We had a dear friend, Dennis, who died of the same brain cancer, but I doubt that he ever once used a cellphone.

Where is the truth about the dangers of using your cellphone? Answer: Nobody really knows, but there are indications that caution is advised.

What is glioblastoma?

Glia comes from the same word in Greek that means glue. Glia refers to several cell types that are not neurons, but which, since their discovery in 1856, have been commonly thought of as the glue that holds your nervous system together. This is true in a sense, but glial cells do more than that.

Its true that glial cells surround neurons everywhere in your body and hold them in place like glue. They are also rich in blood vessels, and so they provide nutrients and oxygen to your neurons. In addition, glial cells form the myelin sheath that surrounds your neurons, insulating one neuron from another and also getting rid of pathogens and dead neurons.

The -oma ending in medical jargon frequently refers to a type of cancer, where cells begin to grow out of control. Blast refers to cells that are precursors to other cells. That is to say that before a particular glial cell comes to be, it is preceded by an undifferentiated cell called a blast. Blastomas begin in blasts.

In the case of glioblastoma, it usually begins in cells that have the potential to differentiate into the type of glial cell called an astrocyte. There are other types of cancer that begin with astrocytes, all called astrocytomas, but glioblastomas account for over half of them.

Glioblastomas are the most invasive of brain tumors in that they grow very rapidly and spread readily to surrounding tissues, making them difficult to remove surgically. They may contain more than one type of cell, so that treating and killing one type of cancerous cell may leave another type to continue growing.

Incidentally, there is also relatively recent research showing that various dysfunctions in your astrocytes may play a role in psychiatric disorders like autism and schizophrenia.

Its about radiation.

Radiation is all around you. Your voice radiates sound waves. A lighted match radiates heat and light waves. The X-ray machine radiates X-radiation. And more.

All of the atoms and molecules in the universe are constantly moving around, jiggling, bumping into things. Heat is the energy that something has because of this movement, and the faster this happens, the more heat is involved. For example, you see water boil because the molecules are moving around and bumping into each other so fast that the original space isnt big enough to contain them.

Sound waves are waves that physically displace air in certain patterns. You hear because of the pattern of the waves of air that enter your ear; without air, there is no sound. The faster the waves arrive at your ear, their frequency, the higher is the pitch you hear. The greater the top-to-bottom height of the waves, the amplitude, the louder is the sound.

Light is an example of electromagnetic radiation, which doesnt require air and is very different from sound and heat, although EMR may cause heat. Rather, EMR consists of perpendicular waves of electricity and magnetism that always travel at the same speed in a vacuum, the speed of light. EMR also behaves as though it were a string of particles, which are called photons. That is, EMR is both immaterial and material simultaneously.

EMR carries a certain amount of energy that is dependent on the frequency of the waves. Low frequency is low energy, and high frequency is high energy. The spectrum of EMR is conventionally divided into segments from low to high energy called radio waves (RF), microwaves, infrared (IR), visible light, ultraviolet, X-rays and gamma rays. A single gamma photon may have 100,000 times as much energy as a red light photon.

Dangers of EMR

Remember that your cells are chock full of DNA, the material that contains your genes, and genes are the biological computer programs that affect much of whats happening in you. A healthy life is critically dependent on your DNA genetic structure having integrity in itself.

As it happens, with exposure to high-energy EMR, like X-rays and gamma rays, a photon can knock an electron off a DNA molecule, ionize it, which can lead to cancer. At lower frequencies, such as RF and microwaves, there is generally not enough energy to disrupt the DNA in that way; the photons are not ionizing.

However, the lower-energy EMR does affect living tissue by generating heat as you may have experienced through sunburn. And youve probably cooked some food using the heat generated by EMR in a microwave oven.

How can your cellphone hurt you?

EMR is all around you: broadcasting radio and TV, Wi-Fi and Bluetooth, microwave cooking, cordless phones, cellphones and towers, satellite phones, and many more.

The problem with the RF and microwave EMR is that they can cause production of compounds called peroxynitrites in your cells. These are derived chemically from nitric oxide, which is an important contributor to your health under normal circumstances. When overactivated by RF radiation, however, NO is a major player in a complex chemical process that results in peroxynitrite damage to your mitochondria.

Mitochondria are those energy producing factors found in most of your cells, and their health is critical to preventing cancer. The most dense concentration of mitochondria you have is in your brain. So while talking on your cellphone, or cordless phone, you are directly applying RF radiation to a most RF-sensitive area of your body.

It was long thought that genetic mutation was the primary cause of cancer. However, research has shown that while genetic mutation is often causative, its only a secondary cause of cancer. The primary cause lies with your mitochondria. That is, mitochondrial damage happens first, and then triggers genetic mutations that may lead to cancer. For more information, see my June 17, 2016, column, The prevention and treatment of cancer.

Research: inconclusive, but suggestive

There has been research into the effects of RF radiation on human health, and especially cancer. Much of the research has been limited and of poor quality, and so its difficult to conclude definitely that cellphone usage will cause cancer.

While not conclusive, however, there is enough credible evidence suggesting a link between cellphones and cancer that the International Agency for Research on Cancer says that RF radiation is a possible human carcinogen. There is a growing body of evidence supporting that link, and urging caution.

How to be cautious

It seems extremely unlikely that we will stop using cell or cordless phones in the foreseeable future. There are, however, several things you can do to minimize your risk of disease from RF radiation.

First, if you must hold the phone to your head, keep your conversations short.

Better yet is to keep the phone away from your body by using its speaker phone feature or by sending text messages instead of having a conversation.

Limit the use of your phone when the reception is weak, three bars or less. The reason is that a weak signal forces your phone to increase the power of its RF signal in order to communicate with the cell tower.

Carry your phone away from your body in a purse or backpack if you can. Separation even as little as an inch between you and the phone antenna can make a big difference in the amount of RF radiation youre receiving.

Its a question mark.

Did McCains cellphone usage cause his brain cancer? We cant know that, and we cant know if your pattern of cellphone and cordless phone usage will damage your health. We do know that there are real risks associated with the use of these phones, and its a simple matter to minimize them.

Bob Keller maintains a holistic pain management practice in Newburyport. His book, Making Sense of Medicine: Medical Matters Made Simple, is available locally or online. He can be reached at 978-465-5111 or bob@myokineast.com.

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Making Sense of Medicine: Is your cellphone killing you? – The Daily News of Newburyport

UVA School of Medicine Using Grant to Research Rare Genetic Disorder – NBC 29 News

CHARLOTTESVILLE, Va. (WVIR) –

The University of Virginia School of Medicine is using a $50,000 donation to further research for an unnamed, rare genetic disorder.The money comes from the Bow Foundation which works to help people affected by the disease.

Right now the disease is fairly new; it was only discovered in the past year and has only 50 known patients.The disorder has mainly been targeting children, and can cause seizures, severe development delays, and movement disorders.

“By making the cells that we’re making from the first patients, we’ll then be able to compare those cells with other researchers and really broaden the research in this field. In a way that wouldn’t be possible without this initial funding, Mike McConnell, UVA professor and researcher, said.

The school says they still know very little about this disease, but the funding is a step in the right direction.

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UVA School of Medicine Using Grant to Research Rare Genetic Disorder – NBC 29 News

Researchers link genes and motor skills development – Medical Xpress

August 10, 2017 Topography of the primary motor cortex, on an outline drawing of the human brain. Different body parts are represented by distinct areas, lined up along a fold called the central sulcus. Credit: public domain

Genes for many may be widely associated with determining certain traits and characteristics. Now a study co-led by John H. Martin of The CUNY School of Medicine at The City College of New York is demonstrating that they could also influence neural motor skills. This could lead to new insights in the treatment of motor skills impairments such as Cerebral Palsy.

Martin and his collaborators from Cincinnati Children’s Hospital Medical Center, Yutaka Yoshida and Zirong Gu, found that the lost function of two genes prevent infant laboratory mice from developing motor skills as they mature into adults. The cause is neural circuits between the brain’s motor cortex region and the spinal cord that did not properly reorganize in mice as they matured. These circuits are part of the cortical spinal network, which coordinates the activation of muscles in limbs.

The mice were bred to lack molecular signaling from the Bax/Bak genetic pathway. Through a variety of experiments, the researchers demonstrated how Bax/Bak’s downstream molecular targets are vital to developing appropriately sophisticated connections between the motor cortex, spinal circuits and opposing extensor/flexor muscle groups in the animals.

“If mutations in the Bax/Bak pathway are found in human patients with developmental motor disabilities, these findings could be very translational and lead to possible medical applications,” said Yoshida, Martin’s co-lead author.

Martin said it is believed that neuronal activity and movement experiences regulate the formation and function of motor circuits as an animal or person matures. “We show that the Bax/Bak pathway is important for this process. This finding may help us better understand the underlying biological mechanisms of motor development,” noted.

The team’s goal is for future studies to determine whether disruptions in Bax/Bak pathway are implicated in some people with skilled motor disabilities and whether it also regulates reorganization of other circuits in the mammalian central nervous system.

The study was published in the journal Neuron.

Explore further: Study suggests genetic reason for impaired skilled movements

Journal reference: Neuron

Provided by: City College of New York

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Researchers link genes and motor skills development – Medical Xpress

Fearing stigmatization, patient’s father seeks retraction of paper on rare genetic mutation – Retraction Watch (blog)

The father of a boy with a rare genetic mutation has accused a scientist of exploiting his child by proclaiming the defect a genetic syndrome and naming it after herself.

At an impasse with scientists investigating, publicizing, and interpreting his sons condition, the father seems willing to use any leverage he can muster to remove the syndrome entry in an online genetic disease database. Based solely on an email he obtained from the database director, the father became convinced that if the paper underpinning the entry were retracted, the syndrome would go down with it. So earlier this year, he withdrew his consent and asked the journal that published the paper for a retraction, based on improper patient consent. He has also threatened to lob accusations of research misconduct at the papers last author.

Marc Pieterse, of The Netherlands, is the father of Vincent, a teenager who has a mutation in the RPS23 gene that has only been found in one other person, so far. In March, an international team of researchers published a paper on Vincents RPS23 mutation in the American Journal of Human Genetics (AJHG), linking it to defective ribosomes, organelles involved in protein synthesis.

One of the scientists Pieterse engaged several years ago is Alyson MacInnes, a rare disease researcher at the University of Amsterdams Academic Medical Center. She is last author of the AJHG paper and the person whose name is now connected to an entry in the Online Mendelian Inheritance in Man (OMIM) database. MacInnes told Retraction Watch that, contrary to what Pieterse claims, she played no direct role in naming the syndrome; OMIM confirmed this account.

The OMIM entry for MacInnes Syndrome, which links the RPS23 mutation with a collection of features that resemble Vincents hearing loss, issues with the hands was created on March 29, weeks after the paper was published. Pieterse said he was shocked when he found it in April as he was browsing the database.

Pieterse told us he feels used and fears that the designation will stigmatize his sons mutation. A syndrome is a disease, he said. Now, he wants the database entry either changed he prefers the umbrella term ribosomopathy, which is used in the paper or taken down.

Believing MacInnes submitted Vincents condition for consideration, Pieterse demanded she find a way to remove it. When she didnt respond, he went directly to AJHG and OMIM to get the paper and syndrome entry removed.

So far, nothing has worked.

A campaign begins

The Pieterses found out about Vincents mutation after a long diagnostic odyssey that ultimately resorted to sequencing all the protein-coding regions of Vincents genome. In 2015, the Journal of the American Medical Association published a news feature on Vincents diagnosis, saying it heralded a new era of clinical genomics.

Marc is a former telecommunications engineer and entrepreneur who has shifted his focus to raising his four children. He told Retraction Watch that although hes not a scientist, in the years since receiving Vincents diagnosis he has committed himself to advocating for further study of the mutation and has even co-authored a paper on RPS23. Marc claims he played a role in connecting MacInnes, Baserga, and several other European scientists, who eventually published the AJHG paper together.

When Pieterse found the OMIM entry for MacInnes syndrome, he believed that MacInnes had created it to boost her career. He told us that after he found it, he tried asking her to take it down. However, their relationship had at that point already suffered a communication breakdown and he didnt hear back. This further upset him and he began a campaign to bring down the entry by any means possible.

But MacInnes told us she had nothing to do with either the OMIM entrys creation or its naming:

I did not submit this paper to OMIM or in any way initiate this entry as a syndrome. This was independently picked up by OMIM and registered as such; apparently such registrations are made upon their decision only.

OMIM director Ada Hamosh confirmed this to Retraction Watch:

Dr. Macinnes did not ask for this to be named after herself and did not bring it to our attention.

We are dealing with this gene-phenotype relationship exactly as we would any other. We did this because this is what we do.

Hamosh, a geneticist at Johns Hopkins University, told us that the term syndrome is for a constellation of features and that the naming was done in accordance with policies that have long been in place at OMIM:

Sometimes something has too many features to be described succinctly. In that case, the default way to name something is to use the first authors last name and last authors last name.

Indeed, Hamosh told us that at first the syndrome was called Paolini-MacInnes syndrome, after first author Nahuel Paolini, of the University of Amsterdam. However, Hamosh said OMIM later realized there were four co-first authors. OMIM never adds more than three names to a syndrome, so Hamosh simply named it after MacInnes:

Given how little we know about it, it makes more sense to name it eponymously than after some features I cant put my hands on, especially since we have a policy on not ever naming something after a gene.

Its stigmatizing

Part of Pieterses issue with dubbing the condition a new syndrome is the early and ongoing nature of RPS23 research, and he isnt alone. In an email to Hamosh, MacInnes co-author Susan Baserga, a professor at the Yale School of Medicine, said:

I was very surprised that you are so pressed to name the phenotype as a new syndrome, especially since the clinical findings are so non-specific. I find this very odd indeed, and worry that it muddles the medical and genetic literature instead of providing clarity. This is so new that I am not even sure that it is a syndrome, and worry that it is presumptuous at best and wrong at worst.

Baserga, who did not respond to our requests for comment, also suggested that OMIM simply call the condition a ribosomopathy, as the AJHG paper does. But Hamosh told Retraction Watch:

We never, ever, ever, name a disease after a gene.

Gene symbols are not stable. More fundamentally, many, many, many genes have more than one condition associated with them. It is not a good idea to put a gene name into a disease name. Thats why we wont call it RPS23 ribosomopathy. Its not personal, we wont do this for any gene.

Pieterse told us that neither Hamosh, nor anybody else from OMIM, has ever informed him that OMIM itself created the entry and that MacInnes Syndrome is the result of standard naming procedures.

Like MacInnes, Hamosh wont respond to his attempt at contact. But Pieterse has obtained an email chain, from late April, between those two scientists, as well as Baserga. In it, Hamosh wrote:

Are you planning to retract or correct the paper to indicate the apparent uncertainty regarding its conclusions? If so, we will remove the phenotype and reclassify the variants.

Niether MacInnes nor Baserga thought a retraction was necessary, but this exchange convinced Pieterse that a retraction would force OMIM to remove the entry. So he wrote MacInnes to inform her he was withdrawing his parental consent and asked AJHG to retract the paper. Pieterse told Retraction Watch that the consent form he submitted to the University of Freiburgs medical center, in Germany (cells used in the study were created there) was very broad and that he believed it would allow him get the paper pulled.

Readers may recall some of the cases weve covered in which patient consent issues have led to papers being retracted. Pieterses situation most closely resembles a story we covered in 2015, where the authors requested a retraction from the Journal of Medical Case Reports after a legal guardian withdrew permission after publication.

But his attempt to trigger retraction didnt work. AJHG editor David Nelson, of the Baylor College of Medicine, told Pieterse the journal had looked into the situation but found nothing improper. According to an email shared by Pieterse, Nelson wrote:

Because there was no reason to retract the article due to misrepresentation of scientific content, we investigated the issues around withdrawal of patient consent. We have been in communication with the [University of Amsterdam Academic Medical Center] Biobank Committee and Medical Ethics Committee and they have confirmed that withdrawal from the study is not relevant to the article and data that have been published already.

Given the serious implications of a retraction on the journal, the authors of the article, and the scientific record, we have therefore decided that the American Journal of Human Genetics will not retract the article.

In an email to Retraction Watch, Nelson expanded on what he told Pieterse:

Our understanding from the authors and their institutions who obtained and approved consent for this study is that it is possible for research subjects to withdraw their consent at any time and that samples and information should be destroyed upon withdrawal. However, published scientific articles deriving from the studies are not subject to the consent withdrawal and this was confirmed by individuals familiar with European Union Regulations relating to personal data.

Pieterse told us that knows a retraction would be counterproductive to his long-term goal, which is to see the research around Vincents mutation grow. But he still wants to see the OMIM entry come down:

At a certain moment, people are going to cite OMIM in genetics papers and its going to spread. If you want to correct something, you should correct it fast. Once the internet is soaked, you cannot do that.

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Fearing stigmatization, patient’s father seeks retraction of paper on rare genetic mutation – Retraction Watch (blog)

How prostate cancer genetics will change front-line care – ModernMedicine

What percentage of prostate cancer cases are caused by genetics?

Most cases of prostate cancer are caused by genetic alterations. The problem is that when you break it down to very specific, identifiable, inherited prostate cancer risk genes, we have very few at the present time. All tumors are driven by genetics, but when you look at specific inherited risk, our current level of understanding is that about 10% to 15% of patients can have a clearly identifiable inherited component to their prostate cancer.

This is a very active area of research. Please talk about whats new and exciting in the world of prostate cancer genetics.

The completion of the Human Genome Project in 2003 opened the door for not only basic science advances but drove the clinical applications of genomic and genetics. Urologists have recently become very familiar with the genomics of prostate tumors studying somatic mutations to help guide treatment decisions. The area we are now becoming interested in is known as germline testing or the study of inherited genetics. Weve been able to identify more and more inherited genetic alterations in medicine. The traditional ones that we have the most familiarity with are the BRCA1 and BRCA2 abnormalities associated with hereditary breast and ovarian cancer. But it turns out that a significant number of men can also have BRCA1 or BRCA2 genetic alterations that can confer an increased risk of prostate cancer.

Also see: Higher reclassification rate seen with saturation biopsy

Several newer genes such as HOXB13 and ATM have also been identified as being associated with prostate cancer. Importantly, were recognizing that not only can prostate cancer run in families but it also can be related to breast cancer, ovarian cancer, pancreatic cancer, melanoma, and Lynch syndrome in other family members. This area of research is giving us some direction on how urologists can think about approaching our patients concerning the need for more detailed family histories.

Lastly, genetic panels are now being offered by commercial laboratories specifically for prostate cancer. Urologists need to be aware that these panels are out there, and the best way to utilize these genetic testing panels is something were all going to have to learn in the coming years.

Originally posted here:

How prostate cancer genetics will change front-line care – ModernMedicine

Center for Genomic Medicine – Massachusetts General …

The Cycle is a paradigm for disease research that begins by comparing human phenotypes and genetic variation to identify genes of importance in human disease, then moves on to characterizing the mechanisms by which the underlying DNA differences lead to disease, and is completed when the knowledge gained delivers benefit back to patients in the forms of improved diagnosis, disease management and treatments.

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Center for Genomic Medicine – Massachusetts General …


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