WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
BRAF
  • Information
  • View History
  • Pending Review
Interpretation 2153
Tier 2
BRAF
Variants
BRAF V600E
Primary Sites
Gall Bladder
Tumor Types
Adenocarcinoma
Interpretation

BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). BRAF mutation frequencies are highly controversial in biliary tract cancers ranging from 0 to 33% for BRAF V600E. As most studies with high BRAF mutation rates were performed on European cohorts, this has raised the question of whether these discordant results represent a regional difference in the genetics of biliary tract cancer. In large cohort of biliary tract cancers including intrahepatic cholangiocarcinomas, extrahepatic cholangiocarcinomas, and adenocarcinomas of the gallbladder, BRAF V600E mutations were only rarely found in intrahepatic cholangiocarcinomas and were not identified in any cases of gallbladder adenocarcinoma. The clinicopathologic significance of BRAF V600E remains to be further elucidated in adenocarcinoma of the gallbladder. Various BRAF inhibitors (Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain settings. These results should be interpreted in the clinical and radiographic context.

Citations
  1. Saetta AA, Papanastasiou P, Michalopoulos NV et al. Mutational analysis of BRAF in gallbladder carcinomas in association with K-ras and p53 mutations and microsatellite instability. Virchows Arch 2004;445:179--182.
  2. Goldenberg D, Rosenbaum E, Argani P et al. The V599E BRAF mutation is uncommon in biliary tract cancers. Mod Pathol 2004;17:1386--1391.
  3. Borger DR, Tanabe KK, Fan KC et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012;17:72--79.
  4. Goeppert B, et al. BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. Mod Pathol. 2014 Jul;27(7):1028-34.
Last updated: 2018-03-30 16:12:50 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use