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Researchers discover new mutations driving malignant melanoma
Date:1/24/2013

BOSTONTwo new mutations that collectively occur in 71 percent of malignant melanoma tumors have been discovered in what scientists call the "dark matter" of the cancer genome, where cancer-related mutations haven't been previously found.

Reporting their findings in the Jan. 24 issue of Science Express, the researchers from Dana-Farber Cancer Institute and the Broad Institute said the highly "recurrent" mutations occurring in the tumors of many people may be the most common mutations in melanoma cells found to date.

The researchers said these cancer-associated mutations are the first to be discovered in the vast regions of DNA in cancer cells that do not contain genetic instructions for making proteins. The mutations are located in non-protein-coding DNA that regulates the activity of genes.

This non-coding DNA, much of which was previously dismissed as "junk," accounts for 99 percent of a cell's genome. A large number of oncogenic mutations in cancer have been identified in the past several decades, but all have been found within the actual genetic blueprints for proteins.

"This new finding represents an initial foray into the 'dark matter' of the cancer genome," said Levi Garraway, MD, PhD, of Dana-Farber and the Broad and the article's senior author.

"In addition, this represents the discovery of two of the most prevalent melanoma gene mutations. Considered as a whole, these two TERT promoter mutations are even more common than BRAF mutations in melanoma. Altogether, this discovery could cause us to think more creatively about the possible benefits of targeting TERT in cancer treatment or prevention."

The mutations affect a promoter region a stretch of DNA code that regulates the expression of a gene adjacent to the TERT gene. TERT contains the recipe for making telomerase reverse transcriptase, an enzyme that can make cells virtually immortal, and is often found overexpressed in cancer c
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

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