January 30, 2012
MD Anderson Melanoma Researchers Identify Predictive Genetic Clues
BY Leslie Loddeke
A study led by Melanoma Medical Oncology Department researcher Michael A. Davies, M.D., Ph.D., published in the journal Cancer identifies significant predictive associations of certain gene mutations with the risk of brain metastasis as well as outcome after diagnosis of stage IV disease.
Davies, senior author of the article, and colleagues at MD Anderson Cancer Center analyzed data collected from 677 melanoma patients who were tested for BRAF and NRAS mutations at MD Anderson Cancer Center.
"This was the largest single-institution study to date to examine the clinical correlations of BRAF and NRAS mutations in patients with advanced melanoma," Davies says. "The study found that the presence of either a BRAF or NRAS mutation correlated with an increased risk of brain metastasis at the time patients were diagnosed with stage IV melanoma," he says. "Similar to a recent study from investigators in Australia, we observed that the presence of a BRAF mutation correlated with aggressive disease in stage IV, but the outcomes of these patients were dramatically improved by treatment with selective BRAF inhibitors, such as the recently FDA-approved vemurafenib."
"However," Davies notes, "we also found that the presence of an NRAS mutation predicts for shorter survival for patients after the diagnosis of stage IV melanoma, as compared to patients with normal ('wild-type') BRAF and NRAS genes."
This novel finding (the Australians did not test for NRAS mutations) "will help us design and interpret future clinical trials appropriately -- and highlights the critical need in melanoma to develop new, more effective treatments for patients with NRAS mutations, which are present in 20% of melanomas."
The identification of such new treatments is one focus of Davies's laboratory research team, along with several other groups at MD Anderson, with funding support from the MD Anderson Specialized Program of Research Excellence (SPORE) grant in melanoma.