While the negative prognostic role of BRAF V600E mutation in metastatic colorectal cancer (mCRC) is well-established, the impact of BRAF codons 594 and 596 mutations, occurring in <1% of CRCs, is completely unknown.
Recent studies at three Italian Institutions suggest that patients with BRAF codons 594 or 596 mutated tumors had markedly longer overall survival (OS) as compared to BRAF V600E mutated. While BRAF V600E mutated tumors were more frequently right-sided, mucinous and with peritoneal spread, BRAF 594 or 596 mutated were more frequently rectal, non mucinous and with no peritoneal spread. All BRAF 594 or 596 mutated tumors were microsatellite stable.
This is consistent with preclinical evidences of a kinase inactivating effect of these mutations. The role of CRAF in transducing the intracellular signal downstream BRAF 594 or 596 mutated proteins opens the way to further preclinical investigation.
