ArticleNature communications2018
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 4 syntheses or guidelines pooled it, 222 citations in OpenAlex.
- Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!Endocrine pathology · 2025Pooled it
- Pooled it
- Well-differentiated G1 and G2 pancreatic neuroendocrine tumors: a meta-analysis of published expanded DNA sequencing data.Frontiers in endocrinology · 2024Pooled it
- Metabolism of pancreatic neuroendocrine tumors: what can omics tell us?Frontiers in endocrinology · 2023Pooled it
- Article
- The Genomic Patterns of Well-Differentiated Pancreatic Neuroendocrine Tumors (NETs) Identify Sub-Sets for Rational Therapeutic Targeting.International journal of molecular sciences · 2026Article
- Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC): An Aggressive Disease Course and Limitations for Personalized Oncology.Oncology and therapy · 2026Article
- Multi-omics profiling of pancreatic neuroendocrine tumors: Interplay of genomic instability and the tumor microenvironment (Review).Oncology letters · 2026Review
- Inhibition of SIRT7 Overcomes Radioresistance in Pancreatic Neuroendocrine Tumors by Reactivating MEN1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Neuroendocrine tumours through an epigenetic lens: Emerging insights for diagnosis and treatment.Journal of neuroendocrinology · 2026Review
- 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
- Survival Outcomes in Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis of Progression-Related Endpoints.Cancers · 2026Review
- Integrated genomics and transcriptomics reveal key events in pancreatic neuroendocrine neoplasm.BMC biology · 2026Article
- Advances in the management of neuroendocrine tumours: Evidence from a systematic review.Biomedical reports · 2026Article
- Molecular taxonomy of pancreatic neuroendocrine tumors reveals BEND2-fusions-driven transcriptional plasticity and therapeutic vulnerabilities.Cell reports. Medicine · 2026Article
- Neuroendocrine Neoplasms of the Gastrointestinal Tract: Morphology, WHO 2022 Grading, and Prognostic Perspectives.Cureus · 2026Review
- Expression of ATRX, DAXX, PDX1, ARX, and somatostatin receptors in pancreatic neuroendocrine tumors: a clinicopathological study.Frontiers in endocrinology · 2026Article
- Somatic mutational profiling identifies aggressive and indolent disease phenotypes in well-differentiated pancreatic neuroendocrine tumors.Frontiers in oncology · 2026Article
72 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
The commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. We genotyped 64 PanNETs and found 58% carry ATRX, DAXX, and MEN1 mutations (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis to reveal two distinct subgroups with one consisting entirely of A-D-M mutant PanNETs. Two genes differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha-cells (FDR q-value < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.