PUBLIC RELEASE DATE:

14-Apr-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. As many as 10 percent of women with a personal or family history of breast or ovarian cancer have at least one genetic mutation that, if known, would prompt their doctors to recommend changes in their care, according to a new study by researchers at the Stanford University School of Medicine.

The women in the study did not have mutations in BRCA1 or BRCA2 (mutations in these genes are strongly associated with hereditary breast and ovarian cancer), but they did have mutations in other cancer-associated genes.

The study was conducted using what's known as a multiple-gene panel to quickly and cheaply sequence just a few possible genetic culprits selected by researchers based on what is known about a disease. Although such panels are becoming widely clinically available, it's not been clear whether their use can help patients or affect medical recommendations.

"Although whole-genome sequencing can clearly be useful under the right conditions, it may be premature to consider doing on everyone," said James Ford, MD, who directs Stanford's Clinical Cancer Genetics Program. "Gene panels offer a middle ground between sequencing just a single gene like BRCA1 that we are certain is involved in disease risk, and sequencing every gene in the genome. It's a focused approach that should allow us to capture the most relevant information."

Ford, an associate professor of medicine and of genetics, is the senior author of the study, which will be published April 14 in the Journal of Clinical Oncology. Allison Kurian, MD, assistant professor of medicine and of health research and policy, and associate director of the Clinical Cancer Genetics Program, is the study's lead author.

Ford was a co-author on a recent paper in the in The Journal of the American Medical Association that highlighted the challenges and opportunities of making whole-genome sequencing clinically available for seemingly healthy people. Although that study showed that whole-genome sequencing can be potentially life-saving, the challenges involved in sequencing the billions of nucleotides that make up all of a person's DNA, and then translating the results into clinical care recommendations, is significant.

"This study indicates that using gene panels to screen for potentially harmful variants can be clinically useful in certain groups of patients," said Kurian. "It also shows that patients, some of whom had given blood samples for research as many as 10 years earlier, are willing and interested to receive this type of follow-up information and to incorporate it into their health care plans."

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Gene panels may be useful, cheaper alternative to whole-genome sequencing, study finds

In order to give patients the most appropriate care, personalised medicine needs to take into account a wide variety of genetic information.

Interview with Mark Hoffman, Director of the Center for Health Insights at the University of Missouri Kansas City, who specialises in bacteriology and personalised medicine, following his lecture entitled Big Data, Little Data and Personalised Medicine during the World of Health (WoHIT 2014) conference which took place in the French city of Nice on 2-4 April.

Mark Hoffman: When we use this term were usually talking about advanced biological testing such as genomics or proteomics (Editors note: study of proteins, particularly their structures and functions in cells and tissue). Personalised medicine basically means using as much information as possible on a patient in order to take the best clinical decision. The aim is to provide the patient with the most appropriate treatment, in accordance with his/her precise genetic information.

Well, the alternative to discrete genetic data is the approach thats in current use a number of written reports and scanned documents, i.e. formats which cannot be read by machines. Discrete genetic test results are stored electronically in a single file. The Electronic Health Record (EHR) pulls these different types of discrete genetic test resultstogether, which should be much more useful for practitioners. As Vice-President at Cerner, I approved an initiative to develop an information system for the laboratory which would generate discrete genetic test results. And this system is now being used in more than 25 genetic testing laboratories worldwide.

The most important innovation will be the use of these various types of genetic tests in clinical practice. We need results which prove how useful these tests are in a clinical situation. And when that happens, the use of the tests will grow and the demand for them from technology platforms will increase.

Well, digital systems protect patient confidentiality better than paper medical files. Access to them can be managed in a far more secure way. So I dont think there are any real issues around the confidentiality of genetic data in patients electronic clinical files. There might perhaps be an exception where the impact of the results of genetic tests goes beyond the individual patients situation. When you learn something about yourself, you realise all the effects this has or might have on those around you your wife, your brother, your aunt, and so on.

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[WoHIT] Use of various types of genetic tests in clinical practice set to be a major innovation

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Newswise (PHILADELPHIA) Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects the lungs, skin and kidneys. Folliculins absence or mutated state has a cascading effect that leads to deteriorated lung integrity and an impairment of lung function, as reported in their findings in the current issue of Cell Reports.

We discovered that without normal FLCN the alveolar epithelial cells (AEC) in these patients lungs began to die, leading to holes in the lungs that grow as increasing numbers of cells disappear. These holes can fill with air and burst, causing the lungs to collapse, says Vera Krymskaya, PhD, MBA, associate professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and researcher in the Airway Biology Initiative of the department of Pulmonary, Allergy and Critical Care.

Between 80 and 100 percent of patients with BHD will develop multiple holes or cysts in the lung.

Healthy human alveoli, the terminal ends of the respiratory tree, are lined with type I and type II alveolar epithelial cells (AECs), a renewable population of progenitors in these distal airspaces. AECs are known to maintain pulmonary alveolar homeostasis by regulating gas exchange and fluid transport in the lungs.

Previous studies have shown that there might be some crosstalk between FLCN and the master energy sensor AMP-activated protein kinase (AMPK). AMPK maintains epithelial cell to cell interactions and is essential for epithelial cell survival. It is regulated through LKB1, a tumor suppressor gene associated with 30 percent of lung cancers. E-cadherin, the zipper molecule that connects epithelial cells, directs LKB1 to cell junctions and its loss impairs LKB1-mediated AMPK activation. This implies that a loss of or mutation in FLCN can trigger a reaction that can impair AMPK activation, epithelial cell to cell interaction and structure, and as a result, promotes cell death.

Penn researchers set out to examine this hypothesis to determine how and why this occurs.

Krymskaya and her team tested both deleted FLCN in mouse lung type II alveolar epithelial cells and mutated FLCN that lacked normal function in both humans with BHD and mouse epithelial cell systems, and compared them with normal human and mouse control cells.

The control cells showed normal epithelial structure, while the mutated FLCN cells showed irregular and disrupted lung cell structure. In addition, the BHD lungs showed very little FLCN in the type II alveolar epithelial cells.

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Penn Researchers Determine Mechanism by Which Lung Function is Regulated in Rare Disease Known As Birt-Hogg-Dube ...

PUBLIC RELEASE DATE:

10-Apr-2014

Contact: Lee-Ann Donegan leeann.donegan@uphs.upenn.edu 215-349-5660 University of Pennsylvania School of Medicine

(PHILADELPHIA) Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects the lungs, skin and kidneys. Folliculin's absence or mutated state has a cascading effect that leads to deteriorated lung integrity and an impairment of lung function, as reported in their findings in the current issue of Cell Reports.

"We discovered that without normal FLCN the alveolar epithelial cells (AEC) in these patients' lungs began to die, leading to holes in the lungs that grow as increasing numbers of cells disappear. These holes can fill with air and burst, causing the lungs to collapse," says Vera Krymskaya, PhD, MBA, associate professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and researcher in the Airway Biology Initiative of the department of Pulmonary, Allergy and Critical Care.

Between 80 and 100 percent of patients with BHD will develop multiple holes or cysts in the lung.

Healthy human alveoli, the terminal ends of the respiratory tree, are lined with type I and type II alveolar epithelial cells (AECs), a renewable population of progenitors in these distal airspaces. AECs are known to maintain pulmonary alveolar homeostasis by regulating gas exchange and fluid transport in the lungs.

Previous studies have shown that there might be some crosstalk between FLCN and the master energy sensor AMP-activated protein kinase (AMPK). AMPK maintains epithelial cell to cell interactions and is essential for epithelial cell survival. It is regulated through LKB1, a tumor suppressor gene associated with 30 percent of lung cancers. E-cadherin, the "zipper" molecule that connects epithelial cells, directs LKB1 to cell junctions and its loss impairs LKB1-mediated AMPK activation. This implies that a loss of or mutation in FLCN can trigger a reaction that can impair AMPK activation, epithelial cell to cell interaction and structure, and as a result, promotes cell death.

Penn researchers set out to examine this hypothesis to determine how and why this occurs.

Krymskaya and her team tested both deleted FLCN in mouse lung type II alveolar epithelial cells and mutated FLCN that lacked normal function in both humans with BHD and mouse epithelial cell systems, and compared them with normal human and mouse control cells.

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Penn study finds mechanism that regulates lung function in disease Birt-Hogg-Dube syndrome

Many who struggle with their weight will often blame a slow metabolism meaning their bodies do not burn calories as quickly or as efficiently as others.

For those who do suffer this condition, investigators from Beth Israel Deaconess Medical Center (BIDMC) say they have found a genetic switch that can accelerate a persons basal metabolic rate leading to a dramatic reduction in the risk for obesity and diabetes.

Their research, published in the journal Nature, involves turning off a gene that encodes a protein called nicotinamide N-methyltransferase (NNMT), which is found in the fat cells and the liver. NNMT is known to process vitamin B3 and has been previously linked with certain types of cancers.

Lead researcher Dr. Barbara Kahn said she and her team first started looking at NNMT in relation to metabolism, after studying a major sugar transporter called GLUT4 in the fat cells of genetically engineered mice. Through their work, they found that mice that produced large amounts of GLUT4 were insulin sensitive and protected against diabetes, while mice with no GLUT4 were insulin resistant and at risk for diabetes.

So we took fat from mice with a lot of this sugar transporter and fat from mice without it, and we did something called a DNA microarray analysis, Kahn, vice chair of the department of medicine at BIDMC and a professor of medicine at Harvard Medical School, told FoxNews.com. We extracted the DNA from the fat tissue and analyzed levels of 16,000 genes at the same time .And we found that the NNMT gene [and the GLUT4 transporter] were the most highly reciprocally regulated. This means that the mice without the GLUT4 transporter had increased levels of NNMT.

Additionally, Kahn and her team analyzed a number of scientific databases and found that high levels of NNMT are often found in the fat cells of animals known to be insulin resistant. Given these findings, the researchers decided to look at NNMT further, to see if manipulating the gene could affect an individuals risk for diabetes and obesity.

In order to lower the expression of the NNMT gene, the researchers used antisense oligonucleotide (ASO) technology, which allowed them to interfere with the expression of the gene only in the fat cells and the liver. ASOs are short molecular strings of DNA, which can be designed to prevent the synthesis of specific proteins.

When the researchers turned off the NNMT gene in mice on high-fat diets, the mice did not gain as much weight compared to when the NNMT gene was functioning normally. Furthermore, the mice did not change their eating or exercise habits, meaning the NNMT solely affected the mices basal metabolic rates.

According to Kahn, NNMT affects a biochemical mechanism known as a futile cycle, which plays a role in metabolic regulation.

If we have an efficient metabolism, we dont need many calories; the cells can get all the energy we need from a small number of calories, Kahn said. If we have an inefficient metabolism, more calories get burned and we can eat more without gaining weight.But when we knock down this NNMT gene, we affect this [futile cycle]. We speed it up, and it will burn up more calories.

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Slow metabolism hindering weight loss? Genetic 'switch' may be answer

Researchers at UNC School of Medicine have pinpointed a viral protein that plays a major role in making respiratory syncytial virus (RSV) the most common cause of hospitalization in children under one year of age.

The discovery, published April 8 in the Journal of Clinical Investigation, is the first step toward identifying better diagnostics and potential treatments for an infection that strikes nearly all children before they reach the age of three and causing severe disease in 3 percent of infected children. RSV infection leads to the hospitalization of between 75,000 and 125,000 babies under one year of age in the United States every year; globally, RSV is the second-leading cause of infant mortality due to infectious disease behind only malaria.

Weve known for a long time that RSV has an increased propensity, compared to other respiratory viruses, for causing obstruction and inflammation in the narrowest airways of the infant lung, leading to severe bronchiolitis, said Raymond Pickles, PhD, associate professor of microbiology and immunology and senior author of the JCI paper. But what weve now shown is that RSV has an increased ability to cause airway obstruction because, during an RSV infection, the virus expresses a specific RSV-encoded non-structural protein, or NS2, in epithelial cells, causing the cells to shed from the airway lining and into the airway lumen. This leads to obstruction of airflow in the small airways and overwhelming inflammation.

According to this study, its this NS2 protein and its effect on epithelial-cell shedding that makes RSV by far the most common cause of bronchiolitis in otherwise healthy young children. The finding was years in the making.

It was a real struggle to put our finger on differences between RSV and other common respiratory viruses that might account for the increased disease caused by RSV, Pickles said. We compared the ability of RSV and parainfluenza virus (PIV3) another common virus in children that causes much less severe airway disease to infect and cause inflammatory responses in a cell culture model of human epithelial cells, which compose the lining of the lung airway. But comparing these consequences of infection did not provide hints as to why RSV and PIV3 produced such differences in disease severity. We did notice, though, that the epithelial cells infected by RSV looked very different during infection compared to those infected by PIV3.

While the PIV-infected epithelial cells retained their natural elongated, columnar shape, the same cells infected with RSV balled up and puffed out of the airway epithelium, causing the infected cells to accumulate in the lumen of the airway. We hypothesized that since RSV and PIV3 are very similar viruses these different effects must be due to differences in the types of genes that RSV expresses, Pickles said.

There arent many genes in RSV, and by generating mutant viruses in the laboratory, Pickles team found that a specific RSV gene the NS2 gene was responsible for the balling up of RSV-infected airway cells. In experiments led by UNC graduate student Rachael Liesman, the researchers decided to engineer PIV3 to express the RSV NS2 gene. When Liesman infected human airway cells in the lab with this re-engineered virus, she saw infected cells ball up and puff out of the airway epithelium. The cells infected by PIV3 expressing the NS2 gene of RSV looked exactly like RSV-infected cells, Liesman said.

Pickles and Liesman then used their reengineered PIV expressing RSV NS2 in animal models to provide more clinical relevance for their findings. They found that infection of the narrowest airways of the lung by PIV3 alone caused moderate levels of inflammation, but after infection by PIV3 expressing RSV NS2, the epithelial cells lining the narrow airways were shed rapidly into the airway lumen. The shedding occurred at such a great rate that the shed cells obstructed the airway lumen, resulting and caused excessive inflammation.

Pickles said that these findings in animal models were almost identical to what has been found in human infants who had died because of RSV infection. Pickles said, Im convinced that the RSV NS2 gene is a major driver for the well-recognized increased ability of RSV to cause lung disease, especially in the extremely narrow small airways of human infants.

Pickles is now on the trail of a human biomarker that would tell doctors if an RSV-infected infant is at greater risk of developing severe lung disease. A biomarker would be key in the development of a needed diagnostic tool and would aid clinical trials that aim to develop anti-RSV therapeutics.

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Genetic trigger found for RSV-induced infant hospitalizations

Print Create a hardcopy of this page Font Size: Default font size Larger font size National Public Health Week now under way Observation recognizes strides made, changes needed in US health system

Posted: Monday, April 7, 2014 11:07 am

Ertel Medicine now offering genetic testing

Ertel Medicine and Pediatrics is now offering special genetic testing called pharmocogenetic testing. The test helps the medical provideradminister the most accurate treatment based on each patients unique science.

Since everyone processes medications differently, this may be the key to help my patientsget to the sweet spot sooner, Dr. Larry Ertel said in a news release. Whether it is Plavix (a heart medicine) which is known to havesevere adverse reactions if the dose is too high or just a common reflux medicine or even anti-depressants I will be able to see how a patient metabolizes medicine and adjust accordingly.

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Ertel Medicine now offering genetic testing

UC Davis School of Veterinary Medicine researchers have identified the genetic mutation responsible for a form of cleft palate in the dog breed Nova Scotia Duck Tolling Retrievers.

They hope that the discovery, which provides the first dog model for the craniofacial defect, will lead to a better understanding of cleft palate in humans. Although cleft palate is one of the most common birth defects in children, affecting approximately one in 1,500 live human births in the United States, it is not completely understood. The findings appear this week online in the journal PLOS Genetics and are available at https://tinyurl.com/knr8wb3.

"This discovery provides novel insight into the genetic cause of a form of cleft palate through the use of a less conventional animal model," said Professor Danika Bannasch, a veterinary geneticist who led the study. "It also demonstrates that dogs have multiple genetic causes of cleft palate that we anticipate will aid in the identification of additional candidate genes relevant to human cleft palate."

Bannasch, who holds the Maxine Adler endowed chair in genetics, explains that common breeding practices have made the dog a unique animal model to help understand the genetic basis of naturally occurring birth defects.

By conducting a genome-wide study of these particular retrievers with a naturally occurring cleft palate, researchers identified a mutation responsible for the development of cleft palate in the breed. Dogs with this mutation also have a shortened lower jaw, similar to humans who have Pierre Robin Sequence. The disorder, a subset of cleft palate, affects one in 8,500 live human births and is characterized by a cleft palate, shortened lower jaw and displacement of the tongue base.

Cleft palate condition occurs when there is a failure in the formation of the secondary palate, which makes up all of the soft palate and the majority of the hard palate. A disruption in the sequential steps of palate development causes a cleft palate and leads to the spectrum of cases that are observed. Children born with cleft palate may develop hearing loss and difficulties with speech and eating. They also may be at increased risk for neurological deficits.

Additional UC Davis researchers include: Zena T. Wolf, a graduate student in the Department of Population Health and Reproduction at the School of Veterinary Medicine, whose thesis topic is the study of craniofacial clefts in dogs; and Assistant Professor Boaz Arzi from the Department of Surgical and Radiological Sciences, School of Veterinary Medicine.

Funding was provided by the Center for Companion Animal Health at the School of Veterinary Medicine and the National Institutes of Health.

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Cleft palate discovery in dogs to aid in understanding human birth defects

Irvine, CA (PRWEB) April 07, 2014

Proove Biosciences, the leader in Personalized Pain Medicine testing services, exhibited and presented research from three studies at the American Society of Interventional Pain Physicians' (ASIPP) 16th annual meeting in New Orleans. The event took place at the Hilton New Orleans Riverside hotel, this weekend, April 4-6.

Proove submitted abstracts on three IRB-approved clinical studies to ASIPP for presentation at the annual meeting. Out of many abstracts submitted by various researchers, ASIPP only accepted 20 studies for presentation and publication. All three Proove study abstracts were accepted for poster presentation, and one of Proove's study abstracts was selected in the "Top 5 Posters" presented before the general session on Saturday afternoon.

Specifically, the company plans to present: Predictive Risk of Injury Complications Enduring Over one Year Using Genetic Predisposition (P.R.I.C.E.) Study, MED Scale to Predict Hydrocodone Efficacy versus the Pain VAS Score Study, and Perception of Analgesia in Narcotic Users with Chronic Pain: A Multi-Center Cross-Sectional Study Comparing Genotype to Pain VAS (P.A.I.N.) Study.

On Saturday afternoon, Proove's Medical Director for Pain and Addiction, Daniel Schwarz, MD, MROC presented information on Prooves P.R.I.C.E. study during the "Top 5 Posters" session.

The PRICE Study demonstrates how a proprietary algorithm can identify workers' compensation claims that are at risk for extending beyond one-year. In this study of 272 patients, a PRICE score of 3 was able to predict claims extending beyond 1 year with an accuracy of 52% positive predictive value (+PPV) and a sensitivity of 88% and specificity of 92%.

The MED Scale to Predict Hydrocodone Efficacy versus the Pain VAS Score Study validates the Proove proprietary MED Scale to identify therapeutic outcomes in pain medicine. This abstract demonstrates how the MED Scale used with chronic non-cancer pain patients taking hydrocodone correlates with the commonly used Pain Visual Analog Scale (VAS). Proove research exhibited findings on how the MED Scale may be a reliable assessment of therapeutic efficacy for chronic pain patients treated with hydrocodone.

The purpose of the PAIN Study is to evaluate whether genotype, or SNP variations can help objectively stratify patient perception of pain among chronic pain patients taking narcotics. Statistical data supports Prooves findings that a proprietary genotypic analysis from Proove can stratify pain perception, and may be a more objective method to define subjective numerical rating scales based on patient perceptions.

ASIPP was created to support the needs of physicians who practice interventional pain management. The society offers extensive opportunities to train and educate physicians on the latest science behind interventional pain management, and is one of the most I involved and influential medical political action groups.

Proove Biosciences is excited to be participating in ASIPPs Annual Meeting, and to share and present our clinical data on how our Proove Genetic tests have been helping to improve clinical outcomes in pain medicine and reducing costs within our healthcare system, stated Brian Meshkin, President of Proove Biosciences and author of the three studies. "Collaborating with our Medical Advisory Board members who are leaders in ASIPP like Dr. Andrea Trescot and Dr. Sandy Silverman, we are very pleased to continue leading the industry in pain medicine genetics testing and research."

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Proove Biosciences Research Recognized and Presented at the American Society of Interventional Pain Physicians 16th ...

Some patients with a suspected genetic disorder will go on what medical professionals call a diagnostic odyssey to find the cause of their symptoms.

A sample is run through the HiSeq 2000, a high-throughput sequencing system in the DNA lab at the University of Iowa Eckstein Medical Research Building in Iowa City. The green dots on the screen show a cluster of the fragment being sequenced. The lab also uses a HiSeq 2500, which can complete sequencing in 27 hours to the HiSeq 2000's 12 days. The Iowa Institute of Human Genetics at the University of Iowa is now offering whole exome sequencing, which is among several initiatives the institute is pursuing to further personalize medicine for patients. (Liz Martin/The Gazette-KCRG)

But those explorations, on occasion, can come up empty, frustrating patients and prompting health care providers to seek outside expertise.

Last month, the Iowa Institute of Human Genetics at the University of Iowa began offering such expertise through whole exome sequencing.

The genetic test, which analyzes a portion of about 20,000 genes in the human genome in hopes of helping practitioners diagnose and treat a patient, is among several initiatives the institute is pursuing to further personalize medicine for patients in Iowa and across the country.

The research we do here is to develop new tests to bring precision medicine to the state, said Colleen Campbell, assistant director of the Iowa Institute of Human Genetics and associate with the UI Department of Otolaryngology.

Researchers with the institute also are conducting tests around secondary findings from exome sequencing the discovery of variants in genes unrelated to a patients primary condition and how a persons genes interact with prescribed medication, including pain medication.

The technology is new, but officials with the Iowa institute said genetic sequencing one day could become so widely used that every infant will have it done as part of the standard newborn screen. Then, as a child grows, practitioners will be able to use the information to determine what type of pain medication to prescribe and at what level, for example.

Our focus is to bring innovation to the state, Campbell said. We want patients to be more informed when they go to the doctor and are offered these new tests. And we want to be able to offer this as a tool to doctors.

The Iowa Institute of Human Genetics is among only a dozen or so institutions nationally that offer whole exome sequencing to physicians wanting to order the test on behalf of a patient.

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University of Iowa hopes to use sequencing to better diagnose and treat patients

New insights on the genetic drivers behind a rare type of fatal pediatric brain cancer may lead to the development of new patient-targeted treatments, a new study suggests.

Each year about 30 children in Canada are diagnosed with diffuse intrinsic pontine glioma (DIPG), a pediatric cancer for which there is no effective treatment.

Because DIPG tumours occur in the middle of the brainstem specifically in the "pons" region that controls vital functions such as breathing, heart regulation and movement doctors are not able to surgically remove them.

As well, biopsies are rarely performed on the tumours, meaning researchers have faced challenges investigating the genetic landscape of DIPG.

But in a new study from Toronto's Hospital for Sick Children, researchers have uncovered the genetic drivers of DIPG.

The study, published online Sunday in the journal Nature Genetics, found that DIPG is comprised of three molecularly distinct subgroups: "MYCN," "silent" and "H3-K27M."

"Although previously considered to be one disease, DIPG represents three distinct subgroups with different methylation, expression, copy number alteration (CAN) and mutational profiles," the authors write.

The results from the study show that DIPG tumours are distinct from adult brain cancer, the study says.

Dr. Cynthia Hawkins, a neuropathologist and the study's principal investigator, said the discovery will have a significant impact on the development of DIPG treatment options.

"This work gives us the opportunity to make some real progress for these patients and their families," she said in a statement.

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New study sheds light on genetic drivers of fatal pediatric cancer

April 5, 2014, 3 a.m.

A genetic test to predict the start of menopause is likely to be available within five years, allowing women to make more informed decisions about their health and fertility, a leading expert says.

A genetic test to predict the start of menopause is likely to be available within five years, allowing women to make more informed decisions about their health and fertility, a leading expert says.

Professor of Reproductive Medicine and Gynaecology at University Medical Centre in the Netherlands, Bart Fauser, said given menopause could begin at very different ages, including before 40 years for about one in 100 women, a test to more precisely predict the timing would be extremely useful, especially for women wanting children.

''The mean age of menopause is 51 but the normal range is between 40 and 60, which is quite considerable 20 years from minimum to maximum means that for some women, ovarian function lasts 50 per cent longer than for others,'' he said.

''Women often postpone having children until their career is well established, but many find it difficult to become pregnant because of declining fertility after the age of 30. Therefore, it would be very useful for women to know well in advance the age gap in which they can expect to remain fertile. This will allow them to try to conceive naturally or to consider egg freezing or IVF treatment at a later date.''

Professor Fauser said a meta-analysis of 22 genetic studies involving almost 39,000 European women found 13 gene variants associated with the age of natural menopause that could be used in testing. The research, published in Nature Genetics in 2012, followed the discovery of four other gene variants that seem to be common among women who experience early or late menopause.

Professor Fauser, who presented his research at the Congress of the Asia Pacific Initiative on Reproduction in Brisbane on Friday, said previous studies had also found that mothers and daughters often experienced menopause at a similar age. While research will continue into the genetics of menopause, he believed a genetic test would be available for women of all ages within five years.

At the moment, women wanting to know more about their fertility can have an ''egg timer'' blood test to measure their levels of Anti-Mullerian Hormone (AMH), a hormone secreted by cells in developing eggs, which are also known as follicles.

Some IVF clinics say the level of AMH in a woman's blood is generally a good indicator of how many fertile years she has left, but some specialists say the test is unreliable.

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Genetic testing to predict menopause

PUBLIC RELEASE DATE:

4-Apr-2014

Contact: Kathy Ridgely Beal, M.B.A. kbeal@acmg.net 301-238-4582 American College of Medical Genetics

Huma Q. Rana, MD of Harvard Medical School's Dana Farber Cancer Institute is the recipient of the 2014 Richard King Trainee Award. This award was instituted five years ago by the ACMG Foundation for Genetic and Genomic Medicine to encourage ABMG or genetic counseling trainees in their careers and to foster the publication of the highest quality research in ACMG's peer-reviewed journal, Genetics in Medicine (GIM). Each year the editorial board reviews all articles published in GIM by an ABMG or genetic counseling trainee who was either a first or corresponding author during that year. The manuscript felt to have the most merit is selected by the editorial board and a cash prize awarded at the 2014 ACMG Annual Clinical Genetics Meeting.

Dr. Rana was given the award for her manuscript titled, " Age-Specific Parkinson Disease Risk in GBA Mutation Carriers: Information for Genetic Counseling" which was published in the February 2013 issue of Genetics in Medicine. The corresponding author was Roy Alcalay, MD, MS of Columbia University.

The award is given by the ACMG Foundation and is named for Dr. Richard King in recognition of his instrumental role in creating Genetics in Medicine and serving as the first and founding Editor-in-Chief of the journal.

Eligible trainees include those in the following programs: Clinical Biochemical Genetics; Clinical Cytogenetics; Clinical Molecular Genetics Combined Internal Medicine/Genetics; Combined Pediatrics/Genetics; PhD Medical Genetics and Genetic Counseling.

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The ACMG Foundation for Genetic and Genomic Medicine, a 501(c)(3) nonprofit organization, is a community of supporters and contributors who understand the importance of medical genetics and genomics and genetic counseling in healthcare. Established in 1992, the ACMG Foundation supports the American College of Medical Genetics and Genomics' mission to "translate genes into health" by raising funds to promote the profession of medical genetics and genomics to medical students, to fund the training of future medical geneticists, to support best-practices and tools for practicing physicians and laboratory directors, to promote awareness and understanding of our work in the general public, and much more.

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Huma Rana, M.D., receives 2014 Richard King Award for best publication, Genetics in Medicine

PUBLIC RELEASE DATE:

4-Apr-2014

Contact: Allison Hydzik hydzikam@upmc.edu 412-559-2431 University of Pittsburgh Schools of the Health Sciences

SAN DIEGO, April 4, 2014 An examination of the genetic landscape of head and neck cancers indicates that while metastatic and primary tumor cells share similar mutations, recurrent disease is associated with gene alterations that could be exquisitely sensitive to an existing cancer drug. Researchers from the University of Pittsburgh Cancer Institute (UPCI) and Yale University School of Medicine will share their findings during a mini-symposium Sunday at the American Association for Cancer Research Annual Meeting 2014.

About 50 percent of patients diagnosed with head and neck squamous cell cancers already have disease that has spread, or metastasized, to the lymph nodes, explained Jennifer Grandis, M.D., distinguished professor and vice chair of research, Department of Otolaryngology, Pitt School of Medicine, and director of the Head and Neck Program at UPCI, partner with UPMC CancerCenter. About 20 to 30 percent of patients thought to be cured of the disease go on to develop recurrent cancer, which typically doesn't respond to standard treatments.

"We decided to compare the genetic signatures of tumor cells from primary tumors with those from disease that had spread and cancers that were thought cured but then came back in the hopes of getting some clues about how best to guide therapy in these different settings," Dr. Grandis said. "We found that recurrent cancers might have an Achilles' heel we can exploit to kill them."

The team conducted the first whole-exome genetic sequencing study on what Dr. Grandis called its "treasure trove" of frozen patient samples and found similar mutations both in primary tumors and in the lymph nodes to which their cancers had already spread. But there were different mutations in tumors that had recurred after a period of remission that were not found in their original cancers.

"The recurrent tumors carried mutations in a gene area that encodes for DDR2 cell receptors," Dr. Grandis said. "Other studies have shown that DDR2 mutations can confer sensitivity to the cancer drug dasatinib, which could mean that drug has promise in the treatment of recurrent head and neck cancers."

The researchers suggest that further investigation of dasatinib treatment is warranted.

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Recurrent head and neck tumors have gene mutations that could be vulnerable to cancer drug

PUBLIC RELEASE DATE:

4-Apr-2014

Contact: Kathy Ridgely Beal, MBA kbeal@acmg.net 301-238-4582 American College of Medical Genetics

Paldeep S. Atwal, MD of Stanford University/Lucile Packard Children's Hospital and Jamie J. Barea, MD, of University of California, San Diego were honored as the 2014-2015 recipients of the Genzyme/ACMG Foundation Medical Genetics Training Award in Clinical Biochemical Genetics at the ACMG 2014 Annual Clinical Genetics Meeting in Nashville, TN.

The objective of the two Genzyme/ACMG Foundation Awards is to support a national training program to encourage the recruitment and training of clinicians in the field of clinical biochemical genetics and especially in the diagnosis, management and treatment of individuals with metabolic diseases. Two awardees are given the opportunity to participate in an in-depth clinical and research experience at a premier medical center with expertise and significant clinical volume in the area of biochemical genetics.

The Award grants $75,000 per year to each of two recipients' institution selected by the ACMG Foundation through a competitive process and will provide for the sponsorship of one year of the trainees' clinical genetics subspecialty in biochemical genetics following residency.

Dr. Atwal received his MD from the University Of Glasgow, Scotland; completed his internal medicine residency with The Royal College of Physicians of the United Kingdom at Glasgow Royal Infirmary, and is currently in the second year of residency in Medical Genetics at Stanford University/Lucile Packard Children's Hospital. His research during the award period will focus on perfecting a novel screening and diagnostic platform for diagnosing lysosomal storage diseases by newborn screening and as a clinical screening tool. He will continue his training as part of the Medical Biochemical Genetics Fellowship Program at Baylor College of Medicine.

"I am humbled to be granted the Genzyme/ACMG Foundation award. I am confident the Medical Biochemical Genetics Fellowship will provide a platform for me to provide the best clinical care possible for patients with inborn errors of metabolism including mitochondrial disorders whilst concurrently conducting translational research."

The second award recipient, Dr. Barea, is currently in his second year of residency in Medical Genetics at University of California- San Diego. He said, "I am honored and excited to be one of the recipients of the Genzyme/ACMG Foundation Award. This award will give me a great opportunity as a Biochemical Genetics fellow at UCSD to gain more knowledge and experience through clinical work and research. This experience will allow me to provide the best possible care for all of my future patients." Dr. Barea completed his MD at Tufts University School of Medicine in Boston, MA and a Pediatrics Residency at University of California, San Diego. His research during the Award period will involve a metabolomic study searching for biomarkers in Gaucher disease and Pompe disease.

"The Genzyme/ACMG Foundation Clinical Genetics Award in Clinical Biochemical Genetics is critical to the development of the genetics workforce. Biochemical genetics is undergoing particularly rapid change, as new insights into disease mechanisms are leading to new methods of treatment," said Bruce R. Korf, MD, PhD, FACMG, president of the ACMG Foundation.

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2014-2015 Genzyme/ACMG Foundation Medical Genetics Training Award announced

April 4, 2014

This puppy is a Nova Scotia Duck Tolling Retriever, the breed with the newly discovered genetic mutation for cleft palate. (Danika Bannasch/UC Davis)

UC Davis School of Veterinary Medicine researchers have identified the genetic mutation responsible for a form of cleft palate in the dog breed Nova Scotia Duck Tolling Retrievers.

They hope that the discovery, which provides the first dog model for the craniofacial defect, will lead to a better understanding of cleft palate in humans. Although cleft palate is one of the most common birth defects in children, affecting approximately one in 1,500 live human births in the United States, it is not completely understood.

The findings appear this week online in the journal PLOS Genetics and are available online at https://tinyurl.com/knr8wb3.

This discovery provides novel insight into the genetic cause of a form of cleft palate through the use of a less conventional animal model, said Professor Danika Bannasch, a veterinary geneticist who led the study. It also demonstrates that dogs have multiple genetic causes of cleft palate that we anticipate will aid in the identification of additional candidate genes relevant to human cleft palate.

Bannasch, who holds the Maxine Adler endowed chair in genetics, explains that common breeding practices have made the dog a unique animal model to help understand the genetic basis of naturally occurring birth defects.

By conducting a genome-wide study of these particular retrievers with a naturally occurring cleft palate, researchers identified a mutation responsible for the development of cleft palate in the breed. Dogs with this mutation also have a shortened lower jaw, similar to humans who have Pierre Robin Sequence. The disorder, a subset of cleft palate, affects one in 8,500 live human births and is characterized by a cleft palate, shortened lower jaw and displacement of the tongue base.

Cleft palate condition occurs when there is a failure in the formation of the secondary palate, which makes up all of the soft palate and the majority of the hard palate. A disruption in the sequential steps of palate development causes a cleft palate and leads to the spectrum of cases that are observed. Children born with cleft palate may develop hearing loss and difficulties with speech and eating. They also may be at increased risk for neurological deficits.

Additional UC Davis researchers include: Zena T. Wolf, a graduate student in the Department of Population Health and Reproduction at the School of Veterinary Medicine, whose thesis topic is the study of craniofacial clefts in dogs; and Assistant Professor Boaz Arzi from the Department of Surgical and Radiological Sciences, School of Veterinary Medicine.

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Cleft palate discovery in dogs to aid in understanding human birth defect

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4-Apr-2014

Contact: Allison Hydzik hydzikam@upmc.edu 412-559-2431 University of Pittsburgh Schools of the Health Sciences

SAN DIEGO, April 4, 2014 Genetic screening of cancer can help doctors customize treatments so that patients with melanoma have the best chance of beating it, according to the results of a clinical trial by researchers at the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter.

The trial, funded by the National Institutes of Health (NIH), will be presented Monday at the American Association for Cancer Research (AACR) Annual Meeting 2014. It showed that the cancer immune therapy drug ipilimumab appears most likely to prevent recurrence in patients whose cancer shows high expression of immune-related genes.

"We've reached a point in the treatment of melanoma and cancer in general where we're making major improvements in the outcomes of patients through personalized medicine," said lead investigator Ahmad Tarhini, M.D., Ph.D., associate professor of medicine and translational science in Pitt's Department of Medicine and Clinical and Translational Science Institute. "Anti-cancer therapy can be associated with significant side effects and economic costs. Therefore, we have a major interest in the development of tests that may allow us to predict which treatment regimen is most likely to help certain patients, while sparing others the unwanted side effects and cost of medications that are unlikely to work."

Before and after ipilimumab treatment, Dr. Tarhini and his colleagues obtained tumor biopsies used to run genetic tests on the tumors of 32 patients with advanced, stage 3 melanoma who were treated by UPMC. All patients were given standard-of-care surgery, which included complete surgical removal of an advanced tumor.

Patients with tumors that had higher levels of expression of a group of immune-related genes, either before or soon after treatment with ipilimumab, had 63 percent lower risk of cancer recurrence after surgery.

"By validating these findings in a large national trial that also will allow us to investigate other significant biomarker data, we'll seek to develop 'biomarker signatures' that doctors can use to customize melanoma treatment plans. The ultimate goals of therapy are to best treat the cancer in an individualized approach, while avoiding the unnecessary exposure of patients to severe side effects," said Dr. Tarhini.

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Genetic testing beneficial in melanoma treatment

Is there a genetic component of this disease?
APFED #39;s Webinar Series Presents... Answers from Experts Is there a genetic component of this disease? John E. Pandolfino, MD Chief, Division of Gastroenterol...

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Is there a genetic component of this disease? - Video

San Francisco, CA (PRWEB) April 02, 2014

CollabRx, Inc. (NASDAQ: CLRX), a data analytics company focused on informing clinical decision-making in molecular medicine, and The Jackson Laboratory (JAX), an independent, nonprofit biomedical research institution with a staff of over 1,500 employees, today announced a multi-year agreement to access CollabRx technology and content resources in support of the clinical interpretation of genetic sequencing-based tests provided by JAX.

The partnership with JAX represents CollabRxs first such relationship with a large and influential non-profit biomedical research institute and demonstrates the companys accelerating pace of business and channel development in 2014. This new milestone attests to the growing adoption of CollabRx technology and interpretive analytics in top-tier laboratories worldwide as a standard aspect of test reporting for clinical genetic sequencing in cancer and other diseases.

The Jackson Laboratory, now in its 85th year, has pioneered the use of genomics and bioinformatics to advance cancer research by bridging basic biology and translational studies to accelerate the development of new therapies, said Thomas Mika, Chairman, President & CEO of CollabRx. We are excited and proud to work with the Laboratory, an NCI-designated Cancer Center, to provide physicians with a clinically relevant interpretation of genetic sequencing test results as a seamless part of the reporting process.

Under the terms of the agreement, CollabRx medical and scientific knowledge will be incorporated into the results of genetic sequencing-based tests in oncology provided by JAX. JAX will leverage CollabRxs dynamically updated knowledge base in molecular medicine, ensuring that the latest medical and scientific data is made available to ordering physicians to aid in their interpretation of test results and inform patient-treatment planning. CollabRxs knowledge base includes the clinical impact of specific genetic profiles and is supported by its large and growing network of over 75 leading clinical practitioners in the United States and Europe.

The partnership will leverage each organizations commitment to developing cutting-edge medical informatics solutions to integrate, automate and standardize molecular testing and reporting in oncology. These capabilities are vital to the large-scale molecular analysis of tumors using clinical genetic sequencing, given the sheer volume and complexity of genetic data that is produced. While genetic sequencing-based tests are increasingly becoming an important part of the clinical management of cancer patients, the resulting explosion of data has outpaced the ability of practicing physicians to understand how to apply this genetic data in treating their patients.

A contextualized interpretation of cancer mutation panels is critical in using a genomics-based approach to inform cancer-treatment planning, said Dr. Charles Lee, Director of the Jackson Laboratory for Genomic Medicine, in Farmington, CT. CollabRx has developed a scalable process and software platform to provide a best-in-class medical informatics solution that will enable JAX to arm physicians with a meaningful analysis of a tumors molecular characteristics when determining a cancer-treatment plan.

About CollabRx CollabRx, Inc. (NASDAQ: CLRX) is a recognized leader in cloud-based expert systems to inform healthcare decision-making. CollabRx uses information technology to aggregate and contextualize the worlds knowledge on genomics-based medicine with specific insights from the nations top cancer experts, starting with the area of greatest need: advanced cancers in patients who have effectively exhausted the standard of care. More information may be obtained at [http://www.collabrx.com .

About The Jackson Laboratory The Jackson Laboratory is an independent, nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine, with a facility in Sacramento, Calif., and a new genomic medicine institute in Farmington, Conn. It employs a total staff of more than 1,500. Its mission is to discover precise genomic solutions for disease and empower the global biomedical community in the shared quest to improve human health. More information may be obtained at [http://www.jax.org/ .

CollabRx Safe Harbor Statement This press release includes forward-looking statements about CollabRxs anticipated results that involve risks and uncertainties. Some of the information contained in this press release, including, but not limited to, statements as to industry trends and CollabRxs plans, objectives, expectations and strategy for its business, contains forward-looking statements that are subject to risks and uncertainties that could cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Any statements that are not statements of historical fact are forward-looking statements. When used, the words "believe," "plan," "intend," "anticipate," "target," "estimate," "expect" and the like, and/or future tense or conditional constructions ("will," "may," "could," "should," etc.), or similar expressions, identify certain of these forward-looking statements. Important factors which could cause actual results to differ materially from those in the forward-looking statements are detailed in filings made by CollabRx with the Securities and Exchange Commission. CollabRx undertakes no obligation to update or revise any such forward-looking statements to reflect subsequent events or circumstances.

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CollabRx and The Jackson Laboratory Partner in Molecular Diagnostics for Cancer

Enabled Reduced Analysis Time Per Case, Improved Ability to Track & Query Identified Variants

BOSTON and LEUVEN, Belgium - Cartagenia, the world leader in software-based workflow support for genetic variant assessment, lab reporting, and integration of diagnostic knowledge-bases, today announced that the Human Genetics Laboratory, part of the Munroe-Meyer Institute for Genetics and Rehabilitation (MMI) at the University of Nebraska Medical Center (UNMC), has selected the Cartagenia Bench platform genetics diagnostics solution for use at its healthcare laboratory. Cartagenia Bench is a cloud-based platform that allows genetics labs and clinicians to analyze, interpret, report, and share genomic variants in routine clinical diagnostics.

Jennifer N. Sanmann, PhD, MB(ASCP)(CM)CG(CM), a representative of the Human Genetics Laboratory at UNMC, noted that its laboratory's adoption of Bench has helped them track their lab findings in a single, well-annotated database and has led to significantly reduced report turnaround times.

"Our laboratory's experience with Cartagenia has been a very positive one," Dr. Sanmann said. "The transition from our internally developed system to Bench CNV and Bench NGS went smoothly and was well supported by the Cartagenia team. It has been our experience that the Bench modules have reduced significantly the amount of analysis time per case and have improved our ability to track and query identified variants."

"The boundary between molecular genetics and cytogenetics testing is fading. NGS technology is being adopted to determine structural events; public registries such as ClinVar collect both CNVs and SNPs; and most importantly, structural variation and molecular variation are more and more often used to jointly explain the patient phenotype, and reach a diagnosis," says Steven Van Vooren, Product Marketing Director at Cartagenia. "At Cartagenia, we strongly believe in a 'single platform' approach, where joint clinical interpretation of structural and molecular events comes natural, and is agnostic of the technology used to pick up variants."

The Cartagenia Bench platform is a clinical-grade, medical device software platform that supports the assesment and reporting of structural variants such as copy number gains, losses, and changes in zygosity, as well as molecular events such as single nucleotide events, and small insertions and deletions.

"We see strong growth in labs adopting both our NGS and CNV modules on the Bench platform, and bringing together structural and molecular variants in their interpretation and reporting," says Herman Verrelst, CEO of Cartagenia. "At Cartagenia, we want to facilitate this evolution, allowing labs to automate their workflow as much as possible and use the time won to focus on the clinical setting in which to assess and report variants - whether postnatal, prenatal or in oncology."

About UNMC

UNMC's Human Genetics Laboratory is a CAP and CLIA accredited full service cytogenetic and molecular genetic laboratory combining comprehensive genetic testing with personalized clinical consultation to provide the very best in genetic medicine to every client and patient served. As genetic disease continues to become more widely identifiable, customized technology and new assays are developed and validated, meeting expanding clinician and patient needs through advancements in systems, software, and diagnoses. In addition to diagnostic and research studies in the areas of perinatal, postnatal, and oncology testing, comprehensive services at UNMC include clinical evaluation by licensed genetic counselors and board certified medical geneticists. Visit unmc.edu/geneticslab to learn more.

About Cartagenia

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University of Nebraska Medical Center Selects Cartagenia Bench Platform for NGS and Array ...