ArticleGenome medicine2022
Whole genome sequencing reveals the independent clonal origin of multifocal ileal neuroendocrine tumors.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- When Histology Is Unknown: Surgical Decision-Making in Small Bowel Tumors-From Preoperative Imaging to Intraoperative Findings: A Narrative Review.Journal of clinical medicine · 2026Review
- Long-term survival and molecular heterogeneity of sporadic multifocal non-functional pancreatic neuroendocrine tumors.iScience · 2026Article
- Tumor count and risk of lymph node metastasis in multiple rectal neuroendocrine tumors: an individual-level pooled analysis.World journal of surgical oncology · 2026Article
- 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
- Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.Molecular cancer · 2026Article
- Acute intestinal obstruction caused by multifocal nodular inflammatory disease of the small intestine: a case report and literature review.BMC surgery · 2026Review
- Identification of divergent PTPN11 mutations in canine histiocytic sarcomas reveals evidence of an independent clonal origin.PloS one · 2026Article
- Controversies in NEN: An ENETS position statement on the treatment of patients with Grade 3 well-differentiated neuroendocrine tumours of the gastro-enteropancreatic tract.Journal of neuroendocrinology · 2025Review
- Characterization of tumor-associated microbiome in multifocal small intestinal neuroendocrine tumors (SI-NETs).ESMO gastrointestinal oncology · 2025Article
- Article
- Small intestinal neuroendocrine tumors lack early genomic drivers, acquire DNA repair defects and harbor hallmarks of low REST expression.Scientific reports · 2025Article
- Non-functional, non-mutated multifocal neuroendocrine neoplasms in a postpartum female: a Case Report of an infrequent disease.Frontiers in medicine · 2025Article
- Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?Endocrine pathology · 2024Review
- Th1 cells inducing IFNγ response improves immunotherapy efficacy in gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023Article
- Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors.Langenbeck's archives of surgery · 2023Article
- Multiomic sequencing of paired primary and metastatic small bowel carcinoids.F1000Research · 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
- Whole genome sequencing reveals the independent clonal origin of multifocal ileal neuroendocrine tumors.Genome medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSmall intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive.
methodsWe performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient.
resultsAbsence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we observed potential loss-of-function gene alterations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors.
conclusionsOur study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.
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