Melanoma: What do all the mutations mean?

Cancer. 2018 Sep 1;124(17):3490-3499. doi: 10.1002/cncr.31345. Epub 2018 Apr 17.

Abstract

Melanoma is one of the most highly mutated malignancies, largely as a function of its generation through ultraviolet light and other mutational processes. The wide array of mutations in both "driver" and "passenger" genes can present a confusing array of data for practitioners, particularly within the context of the recent revolutions in targeted and immune therapy. Although mutations in BRAF V600 clearly confer sensitivity to BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors, the clinical implications of most other mutations are less often discussed and understood. In this review, we provide an overview of the high-frequency genomic alterations and their prognostic and therapeutic relevance in melanoma.

Keywords: BRAF; KIT; NRAS; cyclin-dependent kinase inhibitor 2A (CDKN2A); melanoma; mutation; programmed cell death protein 1 (PD-1).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • GTP Phosphohydrolases / genetics
  • Humans
  • Melanoma / diagnosis*
  • Melanoma / genetics*
  • Melanoma / pathology
  • Membrane Proteins / genetics
  • Mutation / physiology*
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-kit / genetics
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Membrane Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human