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  • Title: Genetic Characteristics of Colorectal Neuroendocrine Carcinoma: More Similar to Colorectal Adenocarcinoma.
    Author: Chen L, Liu M, Zhang Y, Guo Y, Chen MH, Chen J.
    Journal: Clin Colorectal Cancer; 2021 Jun; 20(2):177-185.e13. PubMed ID: 33041225.
    Abstract:
    BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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 BRAFV600E 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). CONCLUSION: CR-NEC has genetic alterations that are more similar to COREAD than other entities. A substantial group of CR-NEC harboring potentially targetable alterations (BRAFV600E) deserves to be tested in clinical practice.
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