ArticleAnnals of surgery2020
Genetic Analysis of Small Well-differentiated Pancreatic Neuroendocrine Tumors Identifies Subgroups With Differing Risks of Liver Metastases.
Article in Annals of surgery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Prognostic factors for the outcome of nonfunctioning pancreatic neuroendocrine tumors in MEN1: a systematic review of literature.Endocrine-related cancer · 2020Pooled it
- Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis.BMC cancer · 2019Pooled it
- Alternative lengthening of telomeres in small well-differentiated pancreatic neuroendocrine tumors: independent validation and cross-platform concordance.Virchows Archiv : an international journal of pathology · 2026Article
- A case of small pancreatic neuroendocrine tumor of less than 10 mm showing metastasis to multiple organs.Clinical journal of gastroenterology · 2026Article
- Real-World-Feasible Immunohistochemistry of ATRX, DAXX, and Menin Identifies a Subgroup of Non-Functioning Pancreatic Neuroendocrine Tumors with low Recurrence Risk to Guide De-Escalating Surveillance.Endocrine pathology · 2026Article
- Long-term survival and molecular heterogeneity of sporadic multifocal non-functional pancreatic neuroendocrine tumors.iScience · 2026Article
- Distinct Malignant Cell States and Myeloid Glutamate Signaling Associated with Aggressive Pancreatic Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Clinicopathological and molecular determinants of pancreatic neuroendocrine tumors: toward precision risk stratification.Journal of translational medicine · 2026Review
- Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape.Molecular cancer · 2026Review
- Prognostic and Predictive Significance of Selected Gene Mutations in Pancreatic and Intestinal Neuroendocrine Tumors.International journal of molecular sciences · 2026Review
- PancreaSeq Genomic Classifier (PancreaSeq GC) Improves Pancreatic Cyst Classification and Detection of Advanced Neoplasia: A Multi-institutional Validation Study.Annals of surgical oncology · 2026Article
- Secretogranin II serves as a potential prognostic biomarker and correlates with the immune microenvironment in pancreatic neuroendocrine tumors.Translational cancer research · 2026Article
- Management of patients with small pancreatic neuroendocrine tumors from a biomarker and surgical perspective.Endocrine-related cancer · 2025Review
- Diagnostic and prognostic biomarkers for pancreatic neuroendocrine neoplasms.Pathologie (Heidelberg, Germany) · 2024Review
- Oncogenic pathway signatures predict the risk of progression and recurrence in well-differentiated pancreatic neuroendocrine tumors.Journal of surgical oncology · 2024Article
- Detecting Somatic Mutations for Well-Differentiated Pancreatic Neuroendocrine Tumors in Endoscopic Ultrasound-Guided Fine Needle Aspiration with Next-Generation Sequencing.Annals of surgical oncology · 2023Article
- Review
- Somatostatin receptor activity assessed byEuropean journal of nuclear medicine and molecular imaging · 2023Article
- Targeted deep sequencing reveals the genetic heterogeneity in well-differentiated pancreatic neuroendocrine tumors with liver metastasis.Hepatobiliary surgery and nutrition · 2023Article
- Maximum Value on Arterial Phase Computed Tomography Predicts Prognosis and Treatment Efficacy of Sunitinib for Pancreatic Neuroendocrine Tumours.Annals of surgical oncology · 2023Article
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveThe aim of this study was to investigate the key molecular alterations in small primary pancreatic neuroendocrine tumors (PanNETs) associated with the development of liver metastases.
backgroundWell-differentiated PanNETs with small size are typically indolent; however, a limited subset metastasize to the liver.
methodsA total of 87 small primary PanNETs (<3 cm), including 32 metastatic cases and 55 nonmetastatic cases after a 5-year follow-up, were immunolabeled for DAXX/ATRX and analyzed for alternative lengthening of telomeres (ALT) by Fluorescence In Situ Hybridization. A subset of these cases, 24 that metastasized and 24 that did not metastasize, were assessed by targeted next-generation sequencing and whole-genome copy number variation.
resultsIn the entire cohort, high Ki-67 (OR 1.369; 95% CI 1.121-1.673; P = 0.002), N-stage (OR 4.568; 95% CI 1.458-14.312; P = 0.009), and ALT-positivity (OR 3.486; 95% CI 1.093-11.115; P = 0.035) were independently associated with liver metastases. In the subset assessed by next-generation sequencing and copy number variation analysis, 3 molecular subtypes with differing risks of liver metastases were identified. Group 1 (n = 15; 73% metastasized) was characterized by recurrent chromosomal gains, CN-LOH, DAXX mutations, and ALT-positivity. Group 2 (n = 19; 42% metastasized, including 5 G1 tumors) was characterized by limited copy number alterations and mutations. Group 3 (n = 14; 35% metastasized) were defined by chromosome 11 loss.
conclusionsWe identified genomic patterns of small PanNETs associated with a different risk for liver metastases. Molecular alterations, such as DAXX mutations, chromosomal gains, and ALT, are associated with an increased risk of metastasis in small PanNETs. Therefore, targeted sequencing and/or ALT analysis may help in the clinical decisions for these small PanNETs.
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