ArticleClinical epigenetics2019
Highly sensitive MLH1 methylation analysis in blood identifies a cancer patient with low-level mosaic MLH1 epimutation.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- Sequencing approaches in hereditary cancer testing: strengths, limitations and future directions.European journal of human genetics : EJHG · 2026Review
- Constitutional methylation of the MLH1 promoter: a case series including tumors not typically caused by Lynch Syndrome.European journal of human genetics : EJHG · 2026Article
- Is Male Infertility an Early Warning of More Serious Diseases?Endocrinology · 2026Review
- Article
- MLH1 c.27G>A (p.Arg9=) is a synonymous likely/pathogenic variant underlying variably mosaic constitutional MLH1 methylation in Lynch syndrome.Familial cancer · 2025Article
- Methylation-sensitive high-resolution melting technology is a simple and sensitive method to detect germline epimutation of the MLH1 gene promoter.Clinical epigenetics · 2025Article
- Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors?JCO precision oncology · 2025Review
- Unraveling noncoding DNA variants and epimutations: a paradigm shift in hereditary cancer research.Future oncology (London, England) · 2024Review
- Testing region selection and prognostic analysis ofGastroenterology report · 2024Article
- Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development.Genome medicine · 2023Article
- 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
- Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers.Clinical epigenetics · 2023Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Assessment of tumor suppressor promoter methylation in healthy individuals.Clinical epigenetics · 2020Article
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Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutional MLH1 methylation (epimutation) is a rare cause of Lynch syndrome. Low-level methylation (≤ 10%) has occasionally been described. This study aimed to identify low-level constitutional MLH1 epimutations and determine its causal role in patients with MLH1-hypermethylated colorectal cancer.Eighteen patients with MLH1-hypermethylated colorectal tumors in whom MLH1 methylation was previously undetected in blood by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were screened for MLH1 methylation using highly sensitive MS-melting curve analysis (MS-MCA). Constitutional methylation was characterized by different approaches.MS-MCA identified one patient (5.6%) with low-level MLH1 methylation (~ 1%) in blood and other normal tissues, which was confirmed by clonal bisulfite sequencing in blood. The patient had developed three clonally related gastrointestinal MLH1-methylated tumor lesions at 22, 24, and 25 years of age. The methylated region in normal tissues overlapped with that reported for other carriers of constitutional MLH1 epimutations. Low-level MLH1 methylation and reduced allelic expression were linked to the same genetic haplotype, whereas the opposite allele was lost in patient's tumors. Mutation screening of MLH1 and other hereditary cancer genes was negative.Herein, a highly sensitive MS-MCA-based approach has demonstrated its utility for the identification of low-level constitutional MLH1 epigenetic mosaicism. The eventual identification and characterization of additional cases will be critical to ascertain the cancer risks associated with constitutional MLH1 epigenetic mosaicism.
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