Monthly Archives: February 2014

A molecular diagnosis gives doctors and patients better treatment options when suspicious lumps are found in the neck.

Genetic biopsy: A Veracyte technician tests 142 genes from patients with suspicious nodules in their thyroid glands.

Later this year, doctors in the U.S. will be able to use a gene test to guide thyroid cancer surgery. The test helps determine when patients harbor a particularly dangerous form of the disease, which can require surgeons to do a second operation on top of the initial diagnostic procedure. Knowing that a patient has this particular form of thyroid cancer could enable surgeons to instead do a single, more extensive surgery.

The company behind the test, Veracyte, already sells a unique genetic assay that helps doctors decide whether to perform surgery on thyroid cancer patients at all. Thyroids that are not cancerous are often removed, which means unnecessary surgery and lifelong hormone replacement therapy for some patients.

Both tests are part of a broader movement in recent years to bring genetic tests into medical care, with oncology leading the way. One test, from Myriad Genetics, looks for mutations linked to increased risk of cancer; others, such as one offered by Foundation Medicine, help doctors prescribe drugs tailored to a particular tumor (see Foundation Medicine: Personalizing Cancer Drugs).

Veracytes first test is the only one that rules out cancer. A lump, or nodule, is caused by growths of cells in the thyroid gland, which is located in the base of the neck. Most often these growths are not cancers. To figure out whether they are, doctors will first take a small needle to extract cells from the lump and then look at the cells under the microscope. And up to 30 percent of the time in U.S. clinics, that test is inconclusive. Because cancer cant be ruled out, typically the next step is to remove the thyroid. The gland normally produces important hormones that regulate metabolism and other body functions, so patients usually then have to take hormone replacement therapy for the rest of their lives.

Between 60 and 80 percent of the time, the nodule in the removed thyroid turns out to be benign. You have unnecessarily put a patient through surgery, says Kishore Lakshman, director of a community thyroid care center in Fall River, Massachusetts. This puts patients at risk for complications such as infection, and creates dependence on hormone therapy. Since 2011, Lakshman has been using Veracytes gene test to assess the risk of cancer in patients whose initial thyroid screen was inconclusive. When I found out that there was a very efficient way of knowing the benign potential of a nodule without exposing a patient to surgery, I was quick to jump on it, says Lakshman.

Veracyte analyzed gene expression levels in hundreds of patients with thyroid nodules, some cancerous, some not, and identified 142 genes that can reliably separate benign from malignant samples. Measuring every gene in the human genome, our scientific team was able to extract genomic information and interpret it with machine-learning algorithms taught to recognize patients with benign nodules, says Bonnie Anderson, CEO and cofounder of the South San Francisco-based company.

The performance of the test was evaluated and published in the New England Journal of Medicine in 2012. That trial showed that Veracytes test can reclassify a nodule from indeterminate to benign 95 percent of the time.

In addition to saving patients from unnecessary surgeries, the test could save significant health-care dollars. A health economics study by Johns Hopkins University School of Medicine researchers found that if the test were used universally in the U.S. for patients whose needle assay was inconclusive, then approximately $122 million in medical costs would be saved each year, primarily because of the significant reduction in surgeries.

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Gene Test Helps Patients Avoid Thyroid Surgery

B.C.-based genome research published this week is expected to help doctors target treatment of lymphoma tumours.

We found novel mutations in a gene that have not been described before in any cancer, said Dr. Christian Steidl, a scientist at the BC Cancer Agency and a professor in the University of British Columbias Department of Pathology who led the study team. Its a first description with a state-of-the-art technology.

Published in the scientific journal Nature Genetics Sunday, the work is part of a worldwide effort to identify gene mutations in all kinds of cancer tumours so treatment can be tailored to an individuals specific illness.

Thats what we mean by personalized medicine, that we dont just use a drug off the shelf and hope it works. Thats what we currently do. We use a drug combination that is very unspecific. It works in a proportion of patients, but we dont really know why.

Projecting five to 10 years in the future, this type of research will be the foundation of the shift that will happen in personalized medicine, said Steidl.

The study took samples from healthy cells and cancer tumours in about 100 patients, which were then analyzed using advanced gene sequencing techniques that have become available in only the last few years. Lead researcher Jay Gunawardana, a PhD student in pathology at UBC, found about 20 per cent of patients with Hodgkins lymphoma and a subtype of non-Hodgkin lymphoma (primary mediastinal B cell lymphoma) carry the same genetic mutation. While there is currently no therapy that can fix the damage caused by this mutation in the gene called PTPN1, experts say it opens the door for other scientists to find a treatment now that the target is known.

The term lymphoma covers about 50 different types of cancer that affect the glands of the lymphatic system that control the bodys immune response. It is divided into two groups, Hodgkin and non-Hodgkin lymphoma, and is the fifth most common cancer type in Canada. Its cause is unknown and it is rising among young adults, according to Lymphoma Canada. Each year, about 8,800 Canadians are diagnosed with lymphoma and more than 3,000 die from the disease.

Dr. Andrew Zelenetz, a lymphoma specialist at Memorial Sloan Kettering Cancer Center in New York who has no connection to the study, said in a telephone interview the discovery is incremental in adding one more piece to the advancement of cancer treatments. But it is a significant contribution to the understanding of lymphoma as diverse rather than a single ailment.

We often mistakenly think of cancer as one thing, that there will be a single magical cure, he said. What genomics has taught us is that we can walk up to three people with the same lymphoma, but if we look inside we see its three different diseases that should be treated in different ways. Today we dont have all the treatment tools that we need, but we would like to get away from having to use poisons as chemotherapy. Wed like to get away from drugs that work non-specifically.

The scale of interest in this area of research can be seen in the International Cancer Genome Consortium which aims to create a catalogue of gene abnormalities found in tumours from 50 different types of cancer. In the U.S., the Cancer Genome Atlas project is focused on specific cancers of the brain, lung and ovary. So far, the missteps in gene coding that cause tumour growth are known in only a tiny fraction of the myriad types of cancer

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New B.C. research lays the groundwork for personalized cancer treatment

Anthony L. Komaroff, M.D. Ask Dr. K

Dr. Komaroff

Dear Dr. K: In yesterday's column, a reader asked whether she should be tested for genes linked to Alzheimer's disease. Today, I thought I'd give you my view on the larger question: Will studies of our genes change the practice of medicine and improve our lives?

My answer: During my career, progress in human genetics has been greater than virtually anyone imagined. However, human genetics also has turned out to be much more complicated than people imagined. As a result, we have not moved as rapidly as we had hoped in changing medical practice.

I graduated from medical school in the late 1960s. We knew what human genes were made of DNA and we were beginning to understand how genes work. We had even identified a handful of genes that were linked to specific diseases. We assumed that disease resulted from an abnormality in the structure of a gene.

If I had asked any biologist on the day I graduated, "Will we ever know how many genes we have, and the exact structure of each gene?" I'll bet the answer would have been: "Not in my lifetime, or my children's lifetime."

They would have been wrong. Today we do know those answers. Indeed, some diseases are caused by an abnormality in the structure of genes. In fact, sometimes it is very simple: one particular change at one particular spot in just one particular gene leads to a specific disease. Sickle cell anemia is an example.

Unfortunately, with most diseases it's far from that simple. The first complexity: Most diseases are influenced by the structure of multiple genes, not just one. Examples are diabetes and high blood pressure.

The second complexity: Many diseases are explained not by an abnormal gene structure, but by whether genes are properly turned on or off. Most cancers fall into this category.

What do I mean by that? Every cell in our body has the same set of genes. Yet, a cell in our eye that sees light is different from a cell in our stomach that makes acid. Why? Because different genes are turned on in each type of cell.

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Ask Dr. K: Gene studies lead to better diagnoses