ArticleGastroenterology2016
Polyclonal Crypt Genesis and Development of Familial Small Intestinal Neuroendocrine Tumors.
Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 35 citations in OpenAlex.
- Spatial Transcriptomics Reveals Location-Specific Tumor Cell Subtypes and Signaling within Multifocal Small Intestinal Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Characterization of small intestinal neuroendocrine tumorlets.Endocrine-related cancer · 2026Article
- Clinical and Pathological Features of EC-cell Familial Small Intestine Neuroendocrine Tumors: A Nationwide Cohort From the French GTE-RENATEN Network.Endocrine pathology · 2026Article
- Single-Cell Comparison of Small Intestinal Neuroendocrine Tumors and Enterochromaffin Cells from Two Patients.Cancers · 2026Article
- Performance of capsule endoscopy for the detection of small intestinal neuroendocrine tumors in familial carcinoid: a prospective single-site study.Gastrointestinal endoscopy · 2024Article
- Article
- Tissue- and cell-specific properties of enterochromaffin cells affect the fate of tumorigenesis toward nonendocrine adenocarcinoma of the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Diagnostic value of whole-mount crypt analysis of ileal biopsy specimens for the patients with familial small intestinal neuroendocrine tumors.Therapeutic advances in medical oncology · 2023Article
- Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine.Nature communications · 2021Article
- Review
- Multifocal Small Bowel Neuroendocrine Tumours.World journal of surgery · 2021Article
- Role of an active reserve stem cell subset of enteroendocrine cells in intestinal stem cell dynamics and the genesis of small intestinal neuroendocrine tumors.American journal of physiology. Gastrointestinal and liver physiology · 2020Review
- Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Not only stem cells, but also mature cells, particularly neuroendocrine cells, may develop into tumours: time for a paradigm shift.Therapeutic advances in gastroenterology · 2018Review
- Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells.Cell stem cell · 2017Article
- Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.Endocrine-related cancer · 2016Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsSmall intestinal neuroendocrine tumors (SI-NETs) are serotonin-secreting well-differentiated neuroendocrine tumors believed to originate from enterochromaffin (EC) cells. Intestinal stem cell (ISC) are believed to contribute to the formation of SI-NETs, although little is known about tumor formation or development. We investigated the relationship between EC cells, ISCs, and SI-NETs.
methodsWe analyzed jejuno-ileal tissue specimens from 14 patients with familial SI-NETs enrolled in the Natural History of Familial Carcinoid Tumor study at the National Institutes of Health from January 2009 to December 2014. Frozen and paraffin-embedded tumor tissues of different stages and isolated crypts were analyzed by in situ hybridization and immunohistochemistry. Tumor clonality was assessed by analyses of mitochondrial DNA.
resultsWe identified multifocal aberrant crypt-containing endocrine cell clusters (ACECs) that contain crypt EC cell microtumors in patients with familial SI-NETs. RNA in situ hybridization revealed expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX, and LGR5(low), in the ACECs and more advanced extraepithelial tumor nests. This expression pattern resembled that of reserve EC cells that express reserve ISC genes; most reside at the +4 position in normal crypts. The presence of multifocal ACECs from separate tumors and in the macroscopic tumor-free mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirmed the independent origin of the ACECs.
conclusionsFamilial SI-NETs originate from a subset of EC cells (reserve EC cells that express reserve ISC genes) via multifocal and polyclonal processes. Increasing our understanding of the role of these reserve EC cells in the genesis of multifocal SI-NETs could improve diagnostic and therapeutic strategies for this otherwise intractable disease.
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