Melanoma genome study implicates sun and new genetic culprits

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The rates of genetic mutations increased along with chronic sun exposure in persons with melanoma, and a new gene has emerged as a potential contributor to disease risk as well, report investigators who sequenced the whole genomes of 25 metastatic melanoma tumors.

“By looking across the entire genome you can more accurately determine the background mutation rate and the different classes of mutations, and more confidently describe the pattern of ultraviolet-induced mutagenesis in melanoma,” explained Michael F. Berger, co-first author of the paper, in a statement announcing his team's findings.

Berger, of the Eli and Edythe L. Broad Institute of Harvard and the Massachusetts Institute of Technology in Cambridge, Massachusetts, and fellow researchers have provided what they call the first high-resolution view of the genomic landscape of human melanoma tumors. Their work, described in a letter published by the journal Nature, has yielded a great deal of data regarding the genetic alterations involved in melanoma.

In addition to discovering that the rates of genetic mutations rose along with chronic sun exposure in patients, thus confirming the role of sun exposure in the development of melanoma, the scientists detected, as expected, the known BRAF and NRAS mutations in 24 of the 25 tumors analyzed. However, they also noted that PREX2 gene was altered in 44% of patients, and in 14% of 107 tumors in a larger validation cohort. PREX2 alterations, already implicated in breast cancer for blocking a tumor-suppressor pathway, were also found to be scattered across the length of the gene in a pattern typically seen when tumor suppressor genes are turned off.

PREX2 may prove to be a therapeutic target in melanoma, and Berger and colleagues also expect to find new melanoma-related genes as they continue to study the whole-genome sequencing data.

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