Comparative analysis of the GNAQ, GNA11, SF3B1, and EIF1AX driver mutations in melanoma and across the cancer spectrum

Pigment Cell Melanoma Res. 2016 Jul;29(4):470-3. doi: 10.1111/pcmr.12482.

Abstract

Uveal melanoma is characterized by recurrent mutations in GNAQ, GNA11, SF3B1, and EIF1AX, as well as a low total mutational burden. The frequency and clinical significance of these mutations in non-uveal melanoma and other cancers is not well described. We identified that GNAQ/GNA11 mutations occur in 0.5–1% of non-uveal melanomas and are essentially melanoma-specific. Further, these mutations are associated with a lack of other typical melanoma mutations (BRAF, NRAS, KIT, NF1), a low mutational burden, and, in a small subset, lack of response to immunotherapy. We suggest that GNAQ/GNA11 mutations characterize an uncommon but distinct subtype of non-uveal melanomas.

Publication types

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

MeSH terms

  • Eukaryotic Initiation Factor-1 / genetics*
  • GTP-Binding Protein alpha Subunits / genetics*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics*
  • Genes, Neoplasm
  • Humans
  • Immunotherapy
  • Melanoma / epidemiology
  • Melanoma / genetics*
  • Melanoma / therapy
  • Mutation*
  • Mutation, Missense
  • Neoplasms / epidemiology
  • Neoplasms / genetics*
  • Phosphoproteins / genetics*
  • Point Mutation
  • Prognosis
  • RNA Splicing Factors / genetics*

Substances

  • Eukaryotic Initiation Factor-1
  • GNA11 protein, human
  • GNAQ protein, human
  • GTP-Binding Protein alpha Subunits
  • Phosphoproteins
  • RNA Splicing Factors
  • SF3B1 protein, human
  • eukaryotic peptide initiation factor-1A
  • GTP-Binding Protein alpha Subunits, Gq-G11