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Ras, Raf, and MAP Kinase in Melanoma

Solus, Jason F. MD; Kraft, Stefan MD

Advances in Anatomic Pathology: July 2013 - Volume 20 - Issue 4 - p 217–226
doi: 10.1097/PAP.0b013e3182976c94
Review Articles

A growing understanding of the biology and molecular mechanisms of melanoma has led to the identification of a number of driver mutations for this aggressive tumor. The most common mutations affect signaling of the Ras/Raf/MAPK (mitogen-activated protein kinase) pathway. This review will focus on mutations in genes encoding proteins that play a role in the MAPK pathway and that have been implicated in melanoma biology, such as BRAF, NRAS, and MEK (MAPK kinase), and detail the current understanding of their role in melanoma progression from a molecular biology perspective. Furthermore, this review will also consider some additional mutations in genes such as KIT, GNAQ, and GNA11, which can be seen in certain subtypes of melanoma and whose gene products interact with the MAPK pathway. In addition, the association of these molecular changes with clinical and classical histopathologic characteristics of melanoma will be outlined and their role in diagnosis of melanocytic lesions discussed. Finally, a basic overview of the current targeted therapy landscape, as far as relevant to the pathologist, will be provided.

Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

The authors have no funding or conflicts of interest to disclose.

Reprints: Stefan Kraft, MD, Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Warren 831, Boston, MA 02114 (e-mail: All figures can be viewed online in color at

© 2013 by Lippincott Williams & Wilkins.