BRAF mutation is associated with the CpG island methylator phenotype in colorectal cancer from young patients.

This study investigated the relationship between BRAF mutation, the CpG island methylator phenotype (CIMP+) and APC methylation in colorectal cancer (CRC) from young patients. The V600E BRAF mutation was found in 7% of cases and was strongly associated with the tumour features of proximal site, advanced stage and poor histological grade. More than half (53%) the tumours with BRAF mutation were also CIMP+ as evaluated by a standard panel of markers, compared to only 4% of tumours with wildtype BRAF (P<0.0001). In contrast to CIMP+, APC methylation was inversely correlated with BRAF mutation (P=0.02). BRAF mutation and CIMP+ are therefore likely to be involved in an alternate, albeit rare, pathway to APC inactivation during the development of CRC in younger patients.