Comprehensive genetic features of gastric mixed adenoneuroendocrine carcinomas and pure neuroendocrine carcinomas

초록

We aimed to determine the pathogenesis of gastric mixed adenoneuroendocrine carcinoma (MANEC) and pure neuroendocrine carcinoma (NEC), which is largely unknown. Targeted DNA sequencing was performed on 34 tumor samples from 21 patients - 13 adenocarcinoma (ADC)/NEC components from MANECs and eight pure NECs - and 21 matched non-neoplastic gastric tissues. Mutational profiles of MANECs/NECs were compared with those of other tumors using public databases. The majority (64.1%; 59/92) of mutations in MANEC were shared by both ADC and NEC components.TP53was the most commonly mutated gene in MANEC (69.2%, 9/13) and pure NEC (87.5%, 8/9). AllTP53mutations in MANEC were pathogenic mutations and were shared by both ADC and NEC components. A subset ofTP53(WT)MANECs had a microsatellite-unstable phenotype or amplifications in various oncogenes includingERBB2andNMYC, and the onlyTP53(WT)pure NEC harboredMYCamplification. Compared to NEC in other organs, NECs arising from the stomach had unique features including less frequentRB1mutations. Differentially altered genes of MANEC ADC components were significantly associated with receptor tyrosine kinase signaling pathways, while differentially altered genes of MANEC NEC components were significantly associated with the NOTCH signaling pathway. Our data provide evidence suggesting a possible clonal origin of ADC and NEC components of MANEC, and we found that gastric MANECs and pure NECs are distinct entities with unique mutational profiles and underlying protein networks. (c) 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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