biostudies-literatureYachida SAMEDCancer Research and Therapeutic Evolution692-711https://www.ebi.ac.uk/biostudies/studies/S-EPMC9394397biostudies-literatureUnknown12(3)The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of NonpanCancer discoveryComprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System.PMC9394397JP21ck0106690JP17cm0106612JP15ck0106138JP21ck0106693JP21ck0106558JP21ck0106547JP20jk0210009JP16ck0106138Takata SSuzuki MFurukawa EHirono SShimomura AMorizane CBrosens LAAHashimoto TShiba SKanda MShibata THorie MKato MWood LDOshima MTotoki YMitsunaga SOkumura THiguchi RRokutan HHackeng WMTanaka HYamamoto MNakamura HYamaue HArihiro KTakai EArai YNoe MNakatani YHruban RHSato TKawasaki KYachida SFurukawa TKiyono TSaito-Adachi MOkano KHama NfalseComprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System.The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpan2022-01-01T00:00:00Z2022 Mar2026-06-06T01:12:50.923Z2025-04-05T21:01:50.91ZS-EPMC93943973488007910.1158/2159-8290.CD-21-0669