Molecular Profiling of Melanoma

Melanoma is a malignant tumor of melanocytes. The disease is the 5^th most common cancer in men and the 7^th in women with an estimated 68,130 new cases and > 8,500 deaths in 2010 (Jemal, 2010). Melanoma is treated with a combination of surgery, chemotherapy, and immunotherapy. Five year survival rates for patients with metastatic disease, unfortunately, are below 10% (Jemal, 2010). Novel therapies and treatment strategies are needed.

Figure 1: Molecular subsets of Melanoma.

Historically, melanoma has been classified according to pathologic and clinical characteristics such as histology (depth, Clark level, ulceration) and anatomic site of origin. Over the past decade, it has become evident that subsets of melanoma can be further defined at the molecular level by recurrent 'driver' mutations that occur in multiple oncogenes, including BRAF, GNA11, GNAQ, KIT, and NRAS (Fig. 1). Such 'driver' mutations lead to constitutive activation of mutant signaling proteins that induce and sustain tumorigenesis.

Mutations in BRAF, GNA11, GNAQ, KIT, and NRAS can be found in approximately 70% of all melanomas. These mutations are seldom found concurrently in the same tumor. The distribution of mutation varies by site of origin and also by the absence or presence of chronic solar damage (Fig. 1). Importantly, targeted small molecule inhibitors are currently available or being developed for specific molecularly defined subsets of patients with melanoma.

The following text is meant to provide a broad overview of several of the oncogenes known to be important for melanoma pathogenesis. Where possible, the presence of a specific mutation is correlated to clinical parameters as well as response to both conventional chemotherapy and targeted agents. At present, only data for treatment of advanced (stage IV) disease is presented.

Author: Christine Lovly, M.D., Ph.D., William Pao, M.D., Ph.D., Jeff Sosman, M.D.

Last updated: February 17, 2012

Disclaimer: The information presented at MyCancerGenome.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.