Driver mutations in melanoma: lessons learned from bench-to-bedside studies.
The identification of somatic driver mutations in human samples has allowed for the development of a molecular classification for melanoma. Recent breakthroughs in the treatment of metastatic melanoma have arisen as a result of these significant new insights into the molecular biology of the disease, particularly the development of inhibitors of activating BRAF(V600E) mutations. In this article the roles of several mutations known to be involved in the malignant transformation of melanocytes are reviewed including BRAF, PTEN, NRAS, ckit, and p16 as well as some of the emerging mutations in cutaneous and uveal melanoma. The bench to bedside collaborations that resulted in these discoveries are summarized, and potential therapeutic strategies to target driver mutations in specific patient subsets are discussed.
The Cancer Institute of New Jersey, 195 Little Albany Street Rm 5543, New Brunswick, NJ 08903, USA. mehnerja@umdnj.edu
Janice M
JM
Mehnert
Harriet M
HM
Kluger
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D016296:Mutagenesis; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D014604:Uveal Neoplasms / Q000235:genetics; D000098943:Uveal Melanoma
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D048493:Proto-Oncogene Proteins B-raf; D051357:Cyclin-Dependent Kinase 2; C446603:TPTE protein, human; D051059:PTEN Phosphohydrolase