Pathology
Mutations in the BRAF gene are found in the majority of cutaneous malignant melanomas and subsets of other tumors. These mutations lead to constitutive activation of BRAF with increased downstream ERK (extracellular signal-regulated kinase) signaling; therefore, the development of RAF kinase inhibitors for targeted therapy is being actively pursued.
germline mutations of BRAF in cardiofaciocutaneous syndrome (CFC syndrome)
somatic activating point mutations of the BRAF oncogene (predominant specific point mutation BRAF-V599E) in
- cutaneous malignant melanomas
- melanocytic nevi with the V600E BRAF mutation (17696195)
- thyroid papillary carcinoma
- primary invasive melanomas (tandem BRAF mutations) (46%) (15140228)
- colorectal adenocarcinoma
- pulmonary adenocarcinoma
- non-Hodgkin lymphomas (2.4%)
- papillary thyroid carcinoma of ovary (struma ovarii) (17721188)
BRAF/AKAP9 fusion gene (15630448)
See also
MAPK signaling pathways
RAS/RAF/MAPK signaling pathway
References
Spittle C, Ward MR, Nathanson KL, Gimotty PA, Rappaport E, Brose MS, Medina A, Letrero R, Herlyn M, Edwards RH. Application of a BRAF pyrosequencing assay for mutation detection and copy number analysis in malignant melanoma. J Mol Diagn. 2007 Sep;9(4):464-71. PMID: 17690212
Schmidt J, Derr V, Heinrich MC, Crum CP, Fletcher JA, Corless CL, Nose V. BRAF in papillary thyroid carcinoma of ovary (struma ovarii). Am J Surg Pathol. 2007 Sep;31(9):1337-43. PMID: 17721188
Bloethner S, Snellman E, Bermejo JL, Hiripi E, Gast A, Thirumaran RK, Wellenreuther R, Hemminki K, Kumar R.Differential gene expression in melanocytic nevi with the V600E BRAF mutation. Genes Chromosomes Cancer. 2007 Aug 15; PMID: 17696195
Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006 Jul;38(7):787-93. PMID: 16804544
Dibb NJ, Dilworth SM, Mol CD. Switching on kinases: oncogenic activation of BRAF and the PDGFR family. Nat Rev Cancer. 2004 Sep;4(9):718-27. PMID: 15343278
Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006 Feb 12; PMID: 16474404