ArticleThe Journal of clinical endocrinology and metabolism2020
Distinct DNA Methylation Signatures in Neuroendocrine Tumors Specific for Primary Site and Inherited Predisposition.
Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!Endocrine pathology · 2025Pooled it
- Article
- Neuroendocrine tumours through an epigenetic lens: Emerging insights for diagnosis and treatment.Journal of neuroendocrinology · 2026Review
- Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape.Molecular cancer · 2026Review
- Gastric Neuroendocrine Tumor Presenting Atypically in von Hippel-Lindau Disease: A Case Report.Journal of kidney cancer and VHL · 2026Article
- Methods in DNA methylation array dataset analysis: A review.Computational and structural biotechnology journal · 2024Review
- Menin in Cancer.Genes · 2024Review
- The Molecular Biology of Midgut Neuroendocrine Neoplasms.Endocrine reviews · 2024Review
- Upregulation of Somatostatin Receptor Type 2 Improves 177Lu-DOTATATE Therapy in Receptor-Deficient Pancreatic Neuroendocrine Tumor Model.Molecular cancer therapeutics · 2023Article
- Multiple Endocrine Neoplasia Type 1 Syndrome Pancreatic Neuroendocrine Tumor Genotype/Phenotype: Is There Any Advance on Predicting or Preventing?Surgical oncology clinics of North America · 2023Review
- An Insight on Functioning Pancreatic Neuroendocrine Neoplasms.Biomedicines · 2023Review
- Epigenetics of Thymic Epithelial Tumors.Cancers · 2023Review
- An update on the development of concepts, diagnostic criteria, and challenging issues for neuroendocrine neoplasms across different digestive organs.Virchows Archiv : an international journal of pathology · 2022Review
- Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors.Frontiers in oncology · 2022Review
- Methionine oxidation of CLK4 promotes the metabolic switch and redox homeostasis in esophageal carcinoma via inhibiting MITF selective autophagy.Clinical and translational medicine · 2022Article
- The landscape of DNA methylation in asthma: a data mining and validation.Bioengineered · 2021Article
- EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine.Scientific reports · 2021Article
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeTo compare the deoxyribonucleic acid (DNA) methylation signature of neuroendocrine tumors (NETs) by primary tumor site and inherited predisposition syndromes von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia type 1 (MEN1).
methodsGenome-wide DNA methylation (835 424 CpGs) of 96 NET samples. Principal components analysis (PCA) and unsupervised hierarchical clustering analyses were used to determine DNA methylome signatures.
resultsHypomethylated CpGs were significantly more common in VHL-related versus sporadic and MEN1-related NETs (P < .001 for both comparisons). Small-intestinal NETs (SINETs) had the most differentially methylated CpGs, either hyper- or hypomethylated, followed by duodenal NETs (DNETs) and pancreatic NETs (PNETs, P < .001 for all comparisons). There was complete separation of SINETs on PCA, and 3 NETs of unknown origin clustered with the SINET samples. Sporadic, VHL-related, and MEN1-related PNETs formed distinct groups on PCA, and VHL clustered separately, showing pronounced DNA hypomethylation, while sporadic and MEN1-related NETs clustered together. MEN1-related PNETs, DNETs, and gastric NETs each had a distinct DNA methylome signature, with complete separation by PCA and unsupervised clustering. Finally, we identified 12 hypermethylated CpGs in the 1A promoter of the APC (adenomatous polyposis coli) gene, with higher methylation levels in MEN1-related NETs versus VHL-related and sporadic NETs (P < .001 for both comparisons).
conclusionsDNA CpG methylation profiles are unique in different primary NET types even when occurring in MEN1-related NETs. This tumor DNA methylome signature may be utilized for noninvasive molecular characterization of NETs, through DNA methylation profiling of biopsy samples or even circulating tumor DNA in the near future.
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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.