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Background  Recent studies emphasize the role of  BRAF  as a genetic marker for prediction, prognosis and risk stratification in colorectal cancer. Earlier studies have reported the incidence of  BRAF  mutations in the range of 5-20% in colorectal carcinomas (CRC) and are predominantly seen in the serrated adenoma-carcinoma pathway characterized by microsatellite instability (MSI-H) and hypermethylation of the MLH1 gene in the setting of the CpG island methylator phenotype (CIMP). Due to the lack of data on the true incidence of  BRAF  mutations in Saudi Arabia, we sought to analyze the incidence of  BRAF  mutations in this ethnic group.    Methods  770 CRC cases were analyzed for  BRAF  and  KRAS  mutations by direct DNA sequencing.    Results   BRAF  gene mutations were seen in 2.5% (19/757) CRC analyzed and  BRAF  V600E somatic mutation constituted 90% (17/19) of all  BRAF  mutations.  BRAF  mutations were significantly associated with right sided tumors (p = 0.0019), MSI-H status (p = 0.0144), CIMP (p = 0.0017) and a high proliferative index of Ki67 expression (p = 0.0162). Incidence of  KRAS  mutations was 28.6% (216/755) and a mutual exclusivity was noted with  BRAF  mutations (p = 0.0518; a trend was seen).    Conclusion  Our results highlight the low incidence of  BRAF  mutations and CIMP in CRC from Saudi Arabia. This could be attributed to ethnic differences and warrant further investigation to elucidate the effect of other environmental and genetic factors. These findings indirectly suggest the possibility of a higher incidence of familial hereditary colorectal cancers especially Hereditary non polyposis colorectal cancer (HNPCC) syndrome /Lynch Syndrome (LS) in Saudi Arabia.

A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma