ArticleScientific reports2023
The genome-wide mutational consequences of DNA hypomethylation.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- RNA Expression Signatures in Glioblastoma: A Systematic Review of Tumour Biology and Therapeutic Targets.Oncology research · 2025Pooled it
- Epigenetic Clocks Can Predict Age in the Largemouth Bass-Complex Despite Spatial and Sexual Variation.Evolutionary applications · 2026Article
- DiffMethylTools: a toolbox for the detection, annotation, and visualization of differential methylation.Life science alliance · 2026Article
- Chemical Exposures, DNA Methylation and Whole Blood DNA Damage in Pet Golden Retrievers.Veterinary and comparative oncology · 2026Article
- Epigenetic Mechanisms of Vitamin D in the Aging Process: A Narrative Review.International journal of molecular sciences · 2026Review
- Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer.Cancer metastasis reviews · 2026Review
- Review
- Conserved and divergent DNA methylation features of extraembryonic tissues between human, mouse and chicken.BMC genomics · 2026Article
- Blood DNA methylation and breast cancer risk: a prospective nested case-control study.EBioMedicine · 2026Article
- Ginsenosides as epigenetic modulators: HDAC, DNMT, and miRNA-targeted mechanisms in tumour suppression.Molecular biology reports · 2026Review
- An Overview of How Epigenetics, MicroRNA-21, and Endocrine Disrupting Compounds Affect Oocyte Maturation and Pre-Implantation Embryo Development.Journal of developmental biology · 2026Review
- Navigating luminal heterogeneity: etiology-based proteogenomic subtyping for targeted treatment strategies in breast cancer.Molecular cancer · 2026Article
- The crosstalk between epigenetics and metabolism in the malignant cell.Discover oncology · 2026Review
- Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.Blood advances · 2026Article
- DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A.PLoS genetics · 2026Article
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- The Future of Epigenetics: Emerging Technologies and Clinical Applications.ACS pharmacology & translational science · 2026Review
- Genome-wide extraction of differentially methylated DNA regions using adapter-anchored proximity primers.Nucleic acids research · 2026Article
- Epigenetics and One-Carbon Metabolism in Cancer: Mechanisms and Therapeutic Implications.Advances in experimental medicine and biology · 2026Review
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
8 more citing papers are in PubMed but not listed here.
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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is important for establishing and maintaining cell identity and for genomic stability. This is achieved by regulating the accessibility of regulatory and transcriptional elements and the compaction of subtelomeric, centromeric, and other inactive genomic regions. Carcinogenesis is accompanied by a global loss in DNA methylation, which facilitates the transformation of cells. Cancer hypomethylation may also cause genomic instability, for example through interference with the protective function of telomeres and centromeres. However, understanding the role(s) of hypomethylation in tumor evolution is incomplete because the precise mutational consequences of global hypomethylation have thus far not been systematically assessed. Here we made genome-wide inventories of all possible genetic variation that accumulates in single cells upon the long-term global hypomethylation by CRISPR interference-mediated conditional knockdown of DNMT1. Depletion of DNMT1 resulted in a genomewide reduction in DNA methylation. The degree of DNA methylation loss was similar to that observed in many cancer types. Hypomethylated cells showed reduced proliferation rates, increased transcription of genes, reactivation of the inactive X-chromosome and abnormal nuclear morphologies. Prolonged hypomethylation was accompanied by increased chromosomal instability. However, there was no increase in mutational burden, enrichment for certain mutational signatures or accumulation of structural variation to the genome. In conclusion, the primary consequence of hypomethylation is genomic instability, which in cancer leads to increased tumor heterogeneity and thereby fuels cancer evolution.
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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.