ArticleBritish journal of cancer2018
Primary constitutional MLH1 epimutations: a focal epigenetic event.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Routes to colorectal cancer in Lynch syndrome: a decade of molecular and clinical insights converging on Schrödinger's cat.Familial cancer · 2026Review
- Germline MLH1 c.-42 C > T is a likely pathogenic variant predisposing to a reduced-penetrance/modified Lynch syndrome phenotype featuring MLH1-methylated cancers.Familial cancer · 2026Article
- Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer.Clinical epigenetics · 2025Article
- Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors?JCO precision oncology · 2025Review
- Deep Learning for Biomarker Discovery in Cancer Genomes.bioRxiv : the preprint server for biology · 2025Article
- Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.Clinical epigenetics · 2024Article
- Constitutional MLH1 Methylation Is a Major Contributor to Mismatch Repair-Deficient, MLH1-Methylated Colorectal Cancer in Patients Aged 55 Years and Younger.Journal of the National Comprehensive Cancer Network : JNCCN · 2023Article
- Multi-omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability.Cancer medicine · 2023Article
- Identification of differentially methylated regions in rare diseases from a single-patient perspective.Clinical epigenetics · 2022Article
- DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden.Frontiers in oncology · 2022Article
- SCTR hypermethylation is a diagnostic biomarker in colorectal cancer.Cancer science · 2020Article
- The missing heritability of familial colorectal cancer.Mutagenesis · 2020Review
- Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.Cancers · 2020Article
- Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma.Clinical epigenetics · 2020Article
- Review
- Highly sensitive MLH1 methylation analysis in blood identifies a cancer patient with low-level mosaic MLH1 epimutation.Clinical epigenetics · 2019Article
- Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer.Cancers · 2019Review
Corrections and comments
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Authors and funding
19 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConstitutional MLH1 epimutations are characterised by monoallelic methylation of the MLH1 promoter throughout normal tissues, accompanied by allele-specific silencing. The mechanism underlying primary MLH1 epimutations is currently unknown. The aim of this study was to perform an in-depth characterisation of constitutional MLH1 epimutations targeting the aberrantly methylated region around MLH1 and other genomic loci.
methodsTwelve MLH1 epimutation carriers, 61 Lynch syndrome patients, and 41 healthy controls, were analysed by Infinium 450 K array. Targeted molecular techniques were used to characterise the MLH1 epimutation carriers and their inheritance pattern.
resultsNo nucleotide or structural variants were identified in-cis on the epimutated allele in 10 carriers, in which inter-generational methylation erasure was demonstrated in two, suggesting primary type of epimutation. CNVs outside the MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as the sole differentially methylated region in MLH1 epimutation carriers compared to controls.
conclusionPrimary constitutional MLH1 epimutations arise as a focal epigenetic event at the EPM2AIP1-MLH1 CpG island in the absence of cis-acting genetic variants. Further molecular characterisation is needed to elucidate the mechanistic basis of MLH1 epimutations and their heritability/reversibility.
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