Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma

J Invest Dermatol. 2007 Apr;127(4):900-5. doi: 10.1038/sj.jid.5700632. Epub 2006 Dec 7.


The BRAF(T1799A) mutation encodes BRAF(V600E) that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAF(T1799A) mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAF(T1799A) mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAF(T1799A) mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAF(T1799A) mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); < or =50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAF(T1799A) mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAF(T1799A) mutation is associated with a lower rate of tumor proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine
  • Child
  • Female
  • Gene Frequency
  • Glutamic Acid
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Melanoma / physiopathology
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Pigmentation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / physiopathology
  • Threonine
  • Valine


  • Threonine
  • Glutamic Acid
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Valine
  • Alanine