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

ells. A promoter region of DNA controls the rate of a gene's transcription the copying of its DNA recipe into a message used by the cell to manufacture a protein.

"We think these mutations in the promoter region are potentially one way the TERT gene can be activated," said Franklin Huang, MD, PhD, co-first author of the report along with Harvard MD-PhD student Eran Hodis, of Dana-Farber and the Broad Institute.

To investigate the mutation's effect, the researchers hooked the mutant TERT promoter to a gene that makes luciferase a light-emitting protein. They observed that the mutant promoter increased the production of luciferase in laboratory cell lines. In the same way, the scientists presume, the mutant promoter in human pigmented skin cells can send the TERT gene into overdrive, potentially contributing to the development of melanoma.

The mutations were discovered when the scientists sifted through data from whole-genome sequencing of malignant melanoma tumors. Unlike "whole-exome" searches that examine only the protein-coding DNA of a cell's genome, whole-genome searches scan all of the DNA, including the non-coding regions.

In analyzing whole-genome data, the investigators discovered the two somatic, or not-inherited, mutations in 17 of 19 (89 percent) of the tumors. Next, they sequenced a larger number of melanoma tumors and found that the two mutations were present in 71 percent of tumors in total.

The researchers said the same mutations are present in cell lines from some other malignancies, and that preliminary evidence showed they might be unusually common in bladder and liver cancers. They also noted that the discovery of these important mutations in DNA previously not linked to cancer-causing alterations highlights the value of whole-genome searches of tumor DNA.


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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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