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BRAF
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Interpretation 102
Tier 1
BRAF
Variants
BRAF V600E
BRAF codon(s) 600 any
BRAF V600D
BRAF V600K
BRAF V600R
BRAF V600M
BRAF V600G
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Presence of a BRAF c.1799T>A, p.Val600Glu (V600E) mutation in a microsatellite unstable colorectal carcinoma indicates that the tumor is probably sporadic and not associated with Lynch syndrome (HNPCC). However, if a BRAF mutation is not detected, the tumor may either be sporadic or Lynch syndrome associated. Detection of BRAF mutations may also be useful in determining patient eligibility for anti-EGFR treatment. Approximately 8--15% of colorectal cancer (CRC) tumors harbor BRAF mutations. The presence of BRAF mutation is significantly associated with right-sided colon cancers and is associated with decreased overall survival. Some studies have reported that patients with metastatic CRC (mCRC) that harbor BRAF mutations do not respond to anti-EGFR antibody agents cetuximab or panitumumab in the chemotherapy-refractory setting. BRAF V600-mutated CRCs may not be sensitive to V600E targeted TKIs. Drug: Vemurafenib + Panitumumab, Encorafenib + Binimetinib + Cetuximab, Radiation + Trametinib + Fluorouracil

Citations
  1. Davies, H., Bignell, G. R., et al. Mutations of the BRAF gene in human cancer. Nature (2002) 417, 949-954.
  2. Di Nicolantonio, F., et al. Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer. J Clin. Oncol. (2008) 26, 5705-5712.
  3. Maestro, M.L. et al. Role of the BRAF Mutations in the Microsatellite Instability Genetic Pathway in Sporadic Colorectal Cancer.Ann. Surg. Oncol. (2007) 14, 1229–1236.
  4. Tol, J. et al. BRAF Mutation in Metastatic Colorectal Cancer. N. Engl. J. Med. (2009) 361, 98-99.
  5. Sharma, S.G., and M.L. Gulley. BRAF mutation testing in colorectal cancer. Arch. Pathol. Lab. Med. (2010) 134, 1225-1228
  6. Prahallad et al.. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR.Nature. 2012 Jan 26;483(7387):100-3.
  7. Gravalos C et al.. Integration of panitumumab into the treatment of colorectal cancer. Crit Rev Oncol Hematol. 2010 Apr;74(1):16-26.
  8. Laurent-Puig P, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 2009;27(35):5924-30
  9. Watanabe M, et al. Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells. Cancer Sci 2013;104(6):687-93
Last updated: 2018-03-15 21:07:15 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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