Sequencing Study Identifies Gene that May Contribute to Melanoma ► NCI Cancer Bulletin for May 15, 2012 - National Cancer Institute

NCI Cancer Bulletin for May 15, 2012 - National Cancer Institute

Sequencing Study Identifies Gene that May Contribute to Melanoma

Also in the News: Sunburn and Indoor Tanning Still Common


Two new reports show that young adults in the United States are engaging in behaviors that increase their risk of skin cancer. Although more people are using sunscreen, staying in the shade, and wearing long clothing down to the ankles to protect themselves from the sun, sunburn remains common, according to the first study; half of all adults 18 to 29 years old reported at least one sunburn in the past year.

A second study found that roughly 30 percent of non-Hispanic white women 18 to 25 years old use indoor tanning devices, greatly increasing their risk of skin cancer.

Both reports appeared in the May 11 Morbidity and Mortality Weekly Report.

A whole-genome sequencing study of metastatic melanoma tumor samples has identified a gene, PREX2, that appears to be commonly mutated in melanoma and may play a role in driving the cancer’s growth and spread. Published online May 9 in Nature, the findings also indicate that rearrangements in chromosomes may contribute to melanoma’s progression and resistance to treatment, the authors wrote.

To conduct the study, Dr. Levi Garraway of Dana-Farber Cancer Institute and Harvard Medical School, and his colleagues from a number of U.S. and European institutions, performed whole-genome sequencing of 25 metastatic melanoma tumor samples and matched healthy tissue from the same patients.

They found that the number of mutated genes varied by the tumor’s location on the body. Tumors in areas that receive little sun exposure had the fewest genetic mutations, whereas those taken from areas that typically receive greater sun exposure had substantially more mutations. A tumor sample taken from a patient with a history of chronic sun exposure had the largest number of mutations.

Chromosomal rearrangements (also called translocations), within the same chromosome and between chromosomes, were common, the authors reported. Given the complexity and location of some of these rearrangements, they “may contribute importantly to melanoma genesis or progression,” the authors wrote.
Chromosomal rearrangements were frequently found near the gene PREX2. Although the most commonly mutated genes were BRAF and RAS, both of which have been linked to melanoma, PREX2 was also commonly mutated. An analysis of an additional 107 melanoma tumor samples confirmed the finding, with approximately 14 percent of the tumors harboring PREX2 mutations.

The researchers also showed that tumor growth was accelerated far more in mice implanted with melanocytes—the pigment-producing cells in which melanoma first develops—with PREX2 mutations than in mice implanted with melanocytes without such mutations.

PREX2 doesn’t appear to fit neatly into the mold of genes typically associated with cancer, they reported. “The pattern of mutations here looks a lot more like a tumor-suppressor gene, but from the functional experiments, it behaved more like an oncogene,” said study co-author Dr. Michael Berger of Memorial Sloan-Kettering Cancer Center in a news release.