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

This study investigated the relationship between BPAF 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.