MAP kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma

Int J Cancer. 2016 May 1;138(9):2257-62. doi: 10.1002/ijc.29970. Epub 2016 Jan 11.

Abstract

Recent therapeutic advances have improved melanoma patientś clinical outcome. Novel therapeutics targeting BRAF, NRAS and cKit mutant melanomas are widely used in clinical practice. However therapeutic options in NRAS(wild-type) /BRAF(wild-type) /cKit(wild-type) melanoma patients are limited. Our study shows that gene copy numbers of members of the MAPK signaling pathway vary in different melanoma subgroups. NRAS(wild-type) /BRAF(wild-type) melanoma metastases are characterized by significant gains of MAP2K1 (MEK1) and MAPK3 (ERK1) gene loci. These additional gene copies could lead to an activation of the MAPK signaling pathway via a gene-dosage effect. Our results suggest that downstream analyses of the pMEK and pERK expression status in NRAS(wild-type) /BRAF(wild-type) melanoma patients identify patients that could benefit from targeted therapies with MEK and ERK inhibitors.

Keywords: BRAF; ERK; MEK; NRAS; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • DNA Mutational Analysis
  • Female
  • GTP Phosphohydrolases / genetics
  • Gene Dosage*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • MAP Kinase Signaling System / genetics*
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Membrane Proteins / genetics
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology

Substances

  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human