ArticleEpigenetics2014
Global hypomethylation and promoter methylation in small intestinal neuroendocrine tumors: an in vivo and in vitro study.
Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
38 citing papers in PubMed, 55 citations in OpenAlex.
- Neuroendocrine tumours through an epigenetic lens: Emerging insights for diagnosis and treatment.Journal of neuroendocrinology · 2026Review
- Prognostic and Predictive Significance of Selected Gene Mutations in Pancreatic and Intestinal Neuroendocrine Tumors.International journal of molecular sciences · 2026Review
- Article
- Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.Scientific reports · 2026Article
- Review
- Loss of MBD2 is associated with tumor growth in small intestinal neuroendocrine tumors.Endocrine connections · 2025Article
- The Molecular Biology of Midgut Neuroendocrine Neoplasms.Endocrine reviews · 2024Review
- Application of Machine Learning in Predicting Hepatic Metastasis or Primary Site in Gastroenteropancreatic Neuroendocrine Tumors.Current oncology (Toronto, Ont.) · 2023Article
- Epigenetic regulation of SSTFrontiers in endocrinology · 2023Article
- Association of LAMA1 Single-Nucleotide Polymorphisms with Risk of Esophageal Squamous Cell Carcinoma among the Eastern Chinese Population.Journal of oncology · 2023Article
- Article
- Article
- Detection of Global DNA Methylation in Cervical Intraepithelial Neoplasia and Cancerous Lesions by Pyrosequencing and Enzyme-Linked Immunosorbent Assays.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine.Scientific reports · 2021Article
- Genetic Drivers of Ileal Neuroendocrine Tumors.Cancers · 2021Review
- Review
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- Alterations of PTEN and SMAD4 methylation in diagnosis of breast cancer: implications of methyl II PCR assay.Journal, genetic engineering & biotechnology · 2021Article
- CBFB-MYH11 Fusion Sequesters RUNX1 in Cytoplasm to Prevent DNMT3A Recruitment to Target Genes in AML.Frontiers in cell and developmental biology · 2021Article
- The multifarious roles of the chemokine CXCL14 in cancer progression and immune responses.Molecular carcinogenesis · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant DNA methylation is a feature of human cancer affecting gene expression and tumor phenotype. Here, we quantified promoter methylation of candidate genes and global methylation in 44 small intestinal-neuroendocrine tumors (SI-NETs) from 33 patients by pyrosequencing. Findings were compared with gene expression, patient outcome and known tumor copy number alterations. Promoter methylation was observed for WIF1, RASSF1A, CTNNB1, CXCL14, NKX2-3, P16, LAMA1, and CDH1. By contrast APC, CDH3, HIC1, P14, SMAD2, and SMAD4 only had low levels of methylation. WIF1 methylation was significantly increased (P = 0.001) and WIF1 expression was reduced in SI-NETs vs. normal references (P = 0.003). WIF1, NKX2-3, and CXCL14 expression was reduced in metastases vs. primary tumors (P<0.02). Low expression of RASSF1A and P16 were associated with poor overall survival (P = 0.045 and P = 0.011, respectively). Global methylation determined by pyrosequencing of LINE1 repeats was reduced in tumors vs. normal references, and was associated with loss in chromosome 18. The tumors fell into three clusters with enrichment of WIF1 methylation and LINE1 hypomethylation in Cluster I and RASSF1A and CTNNB1 methylation and loss in 16q in Cluster II. In Cluster III, these alterations were low-abundant and NKX2-3 methylation was low. Similar analyses in the SI-NET cell lines HC45 and CNDT2 showed methylation for CDH1 and WIF1 and/or P16, CXCL14, NKX2-3, LAMA1, and CTNNB1. Treatment with the demethylating agent 5-azacytidine reduced DNA methylation and increased expression of these genes in vitro. In conclusion, promoter methylation of tumor suppressor genes is associated with suppressed gene expression and DNA copy number alterations in SI-NETs, and may be restored in vitro.
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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.