Despite the increasing incidence rate of colorectal neuroendocrine carcinoma (CR-NEC), there are still few sequencing data to depict the genomic characteristics of CR-NEC.

Next-generation sequencing data of CR-NEC, colorectal adenocarcinoma (COREAD), lung neuroendocrine carcinoma (lung NEC), and gastrointestinal neuroendocrine tumor (GI-NET) were retrieved from the American Association of Cancer Research Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) database platform. Overall survival data of patients were obtained from cBioPortal.

The median tumor mutation burden (TMB) was 5.18 per megabase. TP53 (65.5%), APC (59.5%), KRAS (36.9%), BRAF (20.2%), and RB1 (16.7%) were the most common genes harboring somatic mutations. Nearly all of the BRAF mutations (88.2%) caused V600E. The most common copy number alterations were gain of MYC (12.3%), loss of RB1 (10.7%), and loss of PTEN (5.4%). Compared to lung NEC and GI-NET, the genetic characteristics of CR-NEC were more similar to that of COREAD. CR-NEC had a higher rate of potentially targetable gene alterations compared to lung NEC and GI-NET, and BRAF might be a promising treatment target. Survival analysis indicated that patients with high TMB had significantly worse survival than patients with low TMB (P < .001). In addition, KRAS and RB1 alteration were found to be correlated with worse survival (both P = .023).

CR-NEC has genetic alterations that are more similar to COREAD than other entities. A substantial group of CR-NEC harboring potentially targetable alterations (BRAF) deserves to be tested in clinical practice.