ArticleEuropean journal of human genetics : EJHG2012
MLH1 promoter hypermethylation in the analytical algorithm of Lynch syndrome: a cost-effectiveness study.
Article in European journal of human genetics : EJHG, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- A Systematic Review of Health Economic Evaluations of Diagnostic Biomarkers.Applied health economics and health policy · 2016Pooled it
- Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.Familial cancer · 2014Pooled it
- Uptake of germline testing for Lynch Syndrome in patients with deficient mismatch repair/ microsatellite-high colorectal cancer in the public hospital system in South Australia.Familial cancer · 2026Article
- Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.Nature communications · 2026Article
- Extent of investigation and management of cases of 'unexplained' mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus.Journal of medical genetics · 2024Article
- Testing region selection and prognostic analysis ofGastroenterology report · 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
- Review
- Frequency and clinical features of deficient mismatch repair in ovarian clear cell and endometrioid carcinoma.Journal of gynecologic oncology · 2022Article
- Cancer Risk C (CR-C), a functional genomics test is a sensitive and rapid test for germline mismatch repair deficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- A modified screening strategy for Lynch syndrome among MLH1-deficient CRCs: Analysis from consecutive Chinese patients in a single center.Translational oncology · 2021Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Review
- Highly sensitive MLH1 methylation analysis in blood identifies a cancer patient with low-level mosaic MLH1 epimutation.Clinical epigenetics · 2019Article
- Implication of DNA repair genes in Lynch-like syndrome.Familial cancer · 2019Article
- The Mutator Phenotype: Adapting Microbial Evolution to Cancer Biology.Frontiers in genetics · 2019Review
- Epigenetically Silenced Candidate Tumor Suppressor Genes in Prostate Cancer: Identified by Modeling Methylation Stratification and Applied to Progression Prediction.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Article
- Recent progress in Lynch syndrome and other familial colorectal cancer syndromes.CA: a cancer journal for clinicians · 2018Review
- Personalized medicine in colorectal cancer diagnosis and treatment: a systematic review of health economic evaluations.Cost effectiveness and resource allocation : C/E · 2018Review
- BRCA promoter methylation in sporadic versus BRCA germline mutation-related breast cancers.Breast cancer research : BCR · 2017Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The analytical algorithm of Lynch syndrome (LS) is increasingly complex. BRAF V600E mutation and MLH1 promoter hypermethylation have been proposed as a screening tool for the identification of LS. The aim of this study was to assess the clinical usefulness and cost-effectiveness of both somatic alterations to improve the yield of the diagnostic algorithm of LS. A total of 122 colorectal tumors from individuals with family history of colorectal cancer that showed microsatellite instability and/or loss of mismatch repair (MMR) protein expression were studied. MMR germline mutations were detected in 57 cases (40 MLH1, 15 MSH2 and 2 MSH6). BRAF V600E mutation was assessed by single-nucleotide primer extension. MLH1 promoter hypermethylation was assessed by methylation-specific multiplex ligation-dependent probe amplification in a subset of 71 cases with loss of MLH1 protein. A decision model was developed to estimate the incremental costs of alternative case-finding methods for detecting MLH1 mutation carriers. One-way sensitivity analysis was performed to assess robustness of estimations. Sensitivity of the absence of BRAF mutations for depiction of LS patients was 96% (23/24) and specificity was 28% (13/47). Specificity of MLH1 promoter hypermethylation for depiction of sporadic tumors was 66% (31/47) and sensitivity of 96% (23/24). The cost per additional mutation detected when using hypermethylation analysis was lower when compared with BRAF study and germinal MLH1 mutation study. Somatic hypermethylation of MLH1 is an accurate and cost-effective pre-screening method in the selection of patients that are candidates for MLH1 germline analysis when LS is suspected and MLH1 protein expression is absent.
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