SynthesisFamilial cancer2014
Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.
Synthesis in Familial cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- EMQN best practice guidelines for analysis and reporting of microsatellite instability in solid tumours.European journal of human genetics : EJHG · 2026Guideline
- Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- EPM2 AIP1 immunohistochemistry as a surrogate of promoter methylation analysis in endometrial carcinoma.Virchows Archiv : an international journal of pathology · 2025Article
- Novel microsatellite instability test of sebaceous tumours to facilitate low-cost universal screening for Lynch syndrome.Clinical and experimental dermatology · 2025Article
- Early-stage endometrioid carcinoma with MSH6 protein deficiency: pitfalls in the diagnostic interpretation of microsatellite instability.Frontiers in oncology · 2025Article
- DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications.Cancer medicine · 2025Review
- 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
- Article
- Biomarker characterization in endometrial cancer in Europe: first survey data analysis from 69 pathological academic and hospital labs.Pathologica · 2024Article
- A novel colorectal cancer test combining microsatellite instability andBJC reports · 2024Article
- [Analysis of microsatellite instability in endometrial cancer: The significance of minimal microsatellite shift].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2023Article
- Development and evaluation of INTFrontiers in oncology · 2023Article
- Epigenetic MMR defect identifies a risk group not accounted for through traditional risk stratification algorithms in endometrial cancer.Frontiers in oncology · 2023Article
- Advances in genetic technologies result in improved diagnosis of mismatch repair deficiency in colorectal and endometrial cancers.Journal of medical genetics · 2022Article
- How Should We Test for Lynch Syndrome? A Review of Current Guidelines and Future Strategies.Cancers · 2021Review
- Gynecological Cancers Caused by Deficient Mismatch Repair and Microsatellite Instability.Cancers · 2020Review
- MMR Deficiency is Homogeneous in Pancreatic Carcinoma and Associated with High Density of Cd8-Positive Lymphocytes.Annals of surgical oncology · 2020Article
- High homogeneity of mismatch repair deficiency in advanced prostate cancer.Virchows Archiv : an international journal of pathology · 2020Article
- The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.
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