Researcher Helps Physicians Navigate the Subtleties of Melanoma

The most deadly skin cancer, called melanoma, is on the rise. Clearly, dermatologists and other medical specialists need to be able to distinguish a mole from a melanoma. But now, it is also clear that there are important differences among melanomas. Melanomas are already being grouped into types. However, the conventional classification of melanomas provides little or no information on prognosis or how to treat. In his research at UCSF, Boris Bastian, MD, is making rapid progress in distinguishing moles from cancer and in better defining different types of melanoma in clinically useful ways. Bastian’s work is expected to contribute to the development of treatments tailored to specific forms of the disease. In the future, physicians who treat cancer will be able to routinely order up a genetic profile of melanomas. Physicians will treat each patient individually – using the genetic profile of the tumor that emerges from an analysis of the cancer cells. However, that time has not yet arrived, says Bastian, a UCSF dermatologic oncologist and pathologist. He ought to know. His new melanoma classifications are based in part on the genetic probing of melanomas that he and his UCSF collaborators have undertaken. But analysis of abnormal DNA in melanoma remains primarily a research tools for labs such as Bastian’s. Despite the promise of genetic analysis, Bastian is not looking only at genes. He is looking at how physical or epidemiological characteristics of melanomas are associated with specific genetic abnormalities and with survival. In fact, he has come up with a method that physicians can use to predict with 90 percent accuracy whether melanomas have a certain, particularly important cancer-associated gene mutation – without actually testing for the gene. The overactive, abnormal gene, called BRAF, is found in about half of melanoma cases. The new method develop by Bastian may reach the clinic more quickly than a genetic test, as soon as the next round of research confirms its usefulness. Melanomas with abnormal BRAF are associated with a history of episodic sun exposure, arise most often on the back or trunk, and have a peak incidence among people in their 50s. The BRAF overactivity found in these tumors can be targeted by drugs that are currently in clinical development. In the June edition of the online journal PLoS Medicine, Bastian and his colleagues present findings based on use of the new, non-genetic method. The prediction of a melanoma with abnormal BRAF is based on conventional histopathological analysis, performed during the evaluation of a traditional biopsy, Bastian says. Using this method, pathologists can provide oncologists with an assessment of the likelihood as to whether a given melanoma has the abnormal BRAF gene, according to Bastian. “I think it’s a powerful, interim step before genetic testing becomes broadly available in the clinic,” Bastian says. “We are currently working with the international melanoma community to replicate these findings, to see if the method is robust enough to be incorporated into new guidelines.” In addition to the many melanomas with abnormal BRAF, a smaller number of melanomas – approximately 15 percent – have mutations in another gene, called NRAS. In other melanomas, neither of these two common abnormalities is present. Researchers, therefore, are seeking to identify the additional genes that can go awry and help drive the growth and spread of melanoma, and to develop drugs against them. Bastian and his collaborators have just published a case study further illustrating the importance of identifying and targeting key genetic culprits in individual cases of melanoma. The clinical researchers successfully treated a patient with widespread melanoma in which the tumor cells contained an abnormal form of the gene called KIT. They used an already approved drug, Gleevec. Gleevec, though, has not been successful in treating melanomas driven by other genetic abnormalities. “Our method could help us find other genes that play a role in some of these melanomas,” Bastian says.