ArticleCancer medicine2023
Genetic alterations of GI-NECs involving three main signaling pathways.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Immunological Features of Neuroendocrine Neoplasms and Adrenal Tumors.Cancer medicine · 2026Review
- Prognostic and predictive significance of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas and their utility as an adjunct to accurate diagnosis-An eight-year retrospective study.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Article
- Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas.World journal of gastrointestinal oncology · 2024Article
- Genetic alterations of GI-NECs involving three main signaling pathways.Cancer medicine · 2023Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastrointestinal (GI)-neuroendocrine neoplasms (NENs) are subclassified in neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). The genetic characteristics of GI-NEN has been a hot issue in recent years, but more studies are needed to provide further details. This study aims to provide additional data about genomic characteristics of GI-NENs and the genetic differences between NETs and NECs. PATIENTS AND
methodsThirteen samples were selected for next-generation sequencing (NGS) analysis with a 425-gene panel. Microsatellite instability (MSI) and tumor mutational burden (TMB) were calculated as well as immunohistochemistry (IHC) was used to test for protein expression.
resultsGenetic alterations were very common in NECs, but rare in NETs. The average TMB of NETs and NECs was 2.3 and 6.9, respectively. The TMB of NECs was significantly higher compared to NETs. The TP53 mutation rate was significantly higher in NECs than in NETs (100% vs. 20%), other mutations involved MTOR (n = 2, 15.4%), DDR2 (n = 3, 23.1%), ERBB4 (n = 1, 7.7%), BRCA1 (n = 1, 7.7%), BRCA2 (n = 1, 7.7%), ATM (n = 1, 7.7%), and SMAD4 (n = 1, 7.7%). Deep loss of SMAD4 (1/3, 33.3%), SDHB (1/3, 33.3%), RB1 (1/3, 33.3%), and BRCA2 (1/3, 33.3%), high-level amplification of CRKL (1/3, 33.3%), CCNE1(1/3, 33.3%), and MCL1(1/3, 33.3%) were found in NECs. The integrated analysis found these genetic alterations frequently involve DNA repair and cell cycle, PI3K/AKT/mTOR and TGF-β/SMAD4 signaling pathways.
conclusionGenetic alterations were very common in NECs and rare in NETs, and frequently involved three main signaling pathways. NEC patients harboring these genetic alterations may benefit from targeted therapy and PD-1/PD-L1 immunotherapy.
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