ArticleNature communications2021
DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- nanoASM: Long-Read Allele-Specific DNA Methylation Profiling Enables Functional Annotation of Regulatory Noncoding Variants in Human Prostate Tissues.bioRxiv : the preprint server for biology · 2026Article
- Tumor DNA methylation subtypes predict immunotherapy outcomes in pleural mesothelioma patients in the NIBIT-EPI-MESO study.Nature genetics · 2026Article
- Decitabine Induces Subtype-Specific Epigenomic Remodeling and Perturbs Age-Associated Regulatory CpGs in Breast Cancer.Cancer informatics · 2026Article
- The tumor microenvironment of 14,837 breast cancers is associated with clinical outcome independently of genomic subtypes.Cell reports. Medicine · 2025Article
- Targeted long-read methylation analysis using hybridization capture suitable for clinical specimens.Cell reports methods · 2025Article
- PoreMeth2 for decoding the evolution of methylome alterations with nanopore sequencing.Genome research · 2025Article
- Genome-wide profiling of unmodified DNA using methyltransferase-directed tagging and enrichment.Cell reports methods · 2025Article
- DNA methylation biomarkers for the diagnosis and treatment management of breast cancer: where are we now?Epigenomics · 2025Review
- DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.Nature genetics · 2025Article
- Synthesis, in-vitro,Toxicology research · 2025Article
- Direct genetic transformation bypasses tumor-associated DNA methylation alterations.Genome biology · 2025Article
- A review of the use of tumour DNA methylation for breast cancer subtyping and prediction of outcomes.Clinical epigenetics · 2025Review
- Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers.The Journal of cell biology · 2025Article
- Re-epithelialization of cancer cells increases autophagy and DNA damage: Implications for breast cancer dormancy and relapse.Science signaling · 2025Article
- Cell-type-specific subtyping of epigenomes improves prognostic stratification of cancer.Genome medicine · 2025Article
- Review
- Article
- Case Report: Novel mutation in CHD4 triggers occult breast cancer with bone metastases.Frontiers in oncology · 2025Article
- Liquid biopsy in triple-negative breast cancer: a promising tool for diagnosis, prognosis, and treatment monitoring.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 5 countries.
Funding
Abstract
DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, reduced representation bisulfite sequencing (RRBS) profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis. After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, this study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors.
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