Recurrent mutations of MAPK pathway genes in multiple myeloma but not in amyloid light-chain amyloidosis

Oncotarget. 2016 Oct 18;7(42):68350-68359. doi: 10.18632/oncotarget.12029.

Abstract

Clinically applicable platforms revealing actionable genomic alterations may improve the treatment efficacy of myeloma patients. In this pilot study, we used a high depth targeted sequencing panel containing 83 anti-cancer drug target genes to sequence genomic DNAs extracted from bone marrow aspirates of 23 patients with myeloma and 12 patients with amyloid light-chain (AL) amyloidosis. Mutation analysis revealed NRAS as the most commonly mutated gene (30%, 7/23) in myeloma patients followed by KRAS (26%, 6/23) and BRAF (22%, 5/23). However, no significant mutations were found in the 12 patients with AL amyloidosis. Notably, 6 of the 23 myeloma patients showed multi-site and/or multi-gene mutations in NRAS, KRAS, or BRAF, indicating compound aberrations in the Mitogen activated protein kinase (MAPK) pathway. Gene panel sequencing also revealed cytogenetic abnormalities associated with prognosis in myeloma patients. In conclusion, our pilot study suggests that targeted gene sequencing may have an important prognostic value for myeloma patients for the identification of actionable genomic alterations and cytogenetic aberrations.

Keywords: MAPK pathway; amyloidosis; cancer panel; multiple myeloma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloidosis / genetics*
  • DNA Mutational Analysis / methods
  • Female
  • GTP Phosphohydrolases / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans
  • MAP Kinase Signaling System / genetics*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Mutation*
  • Pilot Projects
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Survival Analysis

Substances

  • KRAS protein, human
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)