Comparative mutational analysis of distal colon cancer with rectal cancer

Distal colon and rectal cancer are associated with each other but display distinct clinical behavior; however, the genetic basis for these differences is poorly understood. In the present study, a systematic comparison of mutational profiles between 137 distal colon and 125 rectal cancer samples was performed based on the data from the Memorial Sloan Kettering Cancer Center. Tumor mutational burden analysis showed that distal colon and rectal cancer harbored a similar burden of ~5.9 mutations/megabase, irrespective of the mismatch repair status. Comparison of significantly mutated genes between the groups determined that B-Raf proto-oncogene serine/threonine kinase mutations were enriched in distal colon cancer, whilst RAS and SMAD family member 4 (SMAD4) mutations were significantly more frequent in rectal cancer. Furthermore, two novel and potentially targetable hotspot mutations (APC regulator of WNT signaling pathway R876* and SMAD4 R361) were identified, which were enriched in rectal cancer compared with distal colon cancer. Overall, the results of the present study showed that the mutation profiles of distal colon and rectal cancer were largely similar, but distinct in specific key genetic events, which may provide valuable information for improving the management of patients with the disease.