Molecular Pathology
Melanoma mutations

Author: Joshua Bradish, M.D. (see Authors page)
Editor: Liang Cheng, M.D.

Revised: 16 November 2015, last major update June 2014

Copyright: (c) 2002-2015,, Inc.

PubMed Search: NRAS [title]

Definition / General
  • NRAS (neuroblastoma RAS viral oncogene homologue) is involved in cell signal transmission
  • NRAS is very similar to HRAS and KRAS in its structure
  • NRAS binds GTP for activation and has GTPase activity for inactivation
  • Activated NRAS can activate both the MAPK pathway and AKT pathway
  • NRAS activates RAF enzymes (ie CRAF or BRAF (Cancer Res 2006;66:9483)
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NRAS pathway

  • Mutated NRAS appears to preferentially activate CRAF over BRAF and my therefore account for some of its associated histological findings
  • NRAS is mostly mutually exclusive with other mutations found in melanoma (i.e. BRAF, KIT, etc) (Cancer Res 2006;66:9483)

  • Associated histological findings
Prognosis and Treatment
  • Multiple commercially available PCR kits are available which detect the most frequent mutations in codons 12, 13, and 61
  • May also detect the full spectrum of mutations through PCR and pyrosequencing

  • Inhibitor therapy
    • No direct inhibitor therapy is currently available but NRAS is an attractive target for future research and development
    • There are several clinical trials currently evaluating the efficacy of MEK inhibition in patients with NRAS mutated melanomas (NRAS Mutations in Melanoma, Vanderbilt-Ingram Cancer Center)
Mechanisms of Resistance
  • No mechanisms of resistance have been described
Resistance Therapies
  • No resistance therapies have been evaluated