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Multiple myeloma study uncovers genetic diversity within tumors
Date:1/13/2014

ly at BRAF, a cancer gene for which several inhibitors, or drugs, exist. Previous studies indicated that around four percent of multiple myeloma patients may have mutations in this gene, and a recent report on a single multiple myeloma patient treated with drugs targeting BRAF showed promising results. BRAF inhibitors have also been used to treat patients with melanoma and other forms of cancer. In the lab, however, the research team found evidence that treating a tumor harboring subclonal BRAF mutations with one of these targeted drugs may at best kill a fraction of the cells, and at worst, stimulate another cancer cell subpopulation to grow.

"There's clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others," said co-first author Jens Lohr an associated scientist at the Broad and a medical oncologist at Dana-Farber. "If a patient has a BRAF mutation in less than 100 percent of his cells, or if he has mutations in KRAS or NRAS at the same time, his oncologist would want to think through the potential pitfalls before giving the inhibitor."

Resistance or the ability for tumors to shrink and then grow back has become a major hurdle in treating patients with targeted therapies such as BRAF inhibitors. The new research suggests that subclonal populations could be one of the potential reasons many patients suffer relapse after treatment.

To take a genetic census of the populations of cancer cells that make up a tumor, the researchers used a computational technique known as ABSOLUTE, developed by the Broad's Cancer Genome Computational Analysis group, led by Broad associate member and co-senior author Gad Getz. In this study, ABSOLUTE was used to analyze information from many samples, but it's also feasible to use the algorithm to analyze information from a single patient. This could allow cancer researchers to examine a specific tumor and determine what fraction of
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Contact: Haley Bridger
hbridger@broadinstitute.org
617-714-7968
Broad Institute of MIT and Harvard
Source:Eurekalert

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