ArticleJournal of medical genetics2014
Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC).
Article in Journal of medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Rate of dissemination and prognosis in early and advanced stage colorectal cancer based on microsatellite instability status: systematic review and meta-analysis.International journal of colorectal disease · 2021Pooled it
- Cytological Features of Pancreatic Medullary Carcinoma Diagnosed by Endoscopic Ultrasound-Guided Fine Needle Aspiration.Diagnostic cytopathology · 2026Article
- DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.Cancer science · 2025Review
- High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.World journal of oncology · 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
- Advances in genetic technologies result in improved diagnosis of mismatch repair deficiency in colorectal and endometrial cancers.Journal of medical genetics · 2022Article
- Article
- Current and Emerging Technologies for the Analysis of the Genome-Wide and Locus-Specific DNA Methylation Patterns.Advances in experimental medicine and biology · 2022Article
- Real-world outcome of universal screening for Lynch syndrome in Japanese patients with colorectal cancer highlights the importance of targeting patients with young-onset disease.Molecular and clinical oncology · 2021Article
- Microsatellite instability (MSI-H) is associated with a high immunoscore but not with PD-L1 expression or increased survival in patients (pts.) with metastatic colorectal cancer (mCRC) treated with oxaliplatin (ox) and fluoropyrimidine (FP) with and without bevacizumab (bev): a pooled analysis of the AIO KRK 0207 and RO91 trials.Journal of cancer research and clinical oncology · 2021Article
- Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status.World journal of clinical oncology · 2021Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients.Gynecologic oncology · 2021Article
- Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative.JCO precision oncology · 2021Article
- The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study.PLoS medicine · 2020Article
- Sebaceoma of a Meibomian Gland of the Upper Eyelid.Ocular oncology and pathology · 2020Article
- Enhanced Tumoral MLH1-Expression in MLH1-/PMS2-Deficient Colon Cancer Is Indicative of Sporadic Colon Cancer and Not HNPCC.Pathology oncology research : POR · 2020Article
- Reliable Clinical MLH1 Promoter Hypermethylation Assessment Using a High-Throughput Genome-Wide Methylation Array Platform.The Journal of molecular diagnostics : JMD · 2020Article
- MSH6 immunohistochemical heterogeneity in colorectal cancer: comparative sequencing from different tumor areas.Human pathology · 2020Article
- Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome.Journal of medical genetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsLynch syndrome (LS) patients have DNA mismatch repair deficiency and up to 80% lifetime risk of colorectal cancer (CRC). Screening of mutation carriers reduces CRC incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour-derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from LS (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations.
methodsTumour DNA was extracted (formalin fixed, paraffin embedded, FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared. FINDINGSS: Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2% to 98.4%), specificity 87.7% (95% CI 77.9% to 94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7% to 76.5%), specificity 98.6% (95% CI 92.4% to 100.0%) for the identification of those with pathogenic MLH1 mutations.
conclusionsQuantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.