ArticleBMJ open2016
Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort.
Article in BMJ open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Microsatellite status and its correlation with clinicopathological features in gastric carcinoma: insights from a retrospective study in Northern Pretoria.Pathology oncology research : POR · 2026Article
- Genotype-phenotype correlations in carriers of the PMS2 founder variant c.1831dup.Molecular genetics & genomic medicine · 2024Article
- DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology.International journal of molecular sciences · 2023Review
- A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.Journal of translational medicine · 2023Article
- Lynch syndrome, molecular mechanisms and variant classification.British journal of cancer · 2023Review
- A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.medRxiv : the preprint server for health sciences · 2023Article
- Evaluating Multiple Next-Generation Sequencing-Derived Tumor Features to Accurately Predict DNA Mismatch Repair Status.The Journal of molecular diagnostics : JMD · 2023Article
- Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy in Patients With Metastatic Colorectal Cancer With Measures of Microsatellite Instability, Mismatch Repair, or Tumor Mutational Burden.JAMA network open · 2023Article
- A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric-cancer patients.Gastroenterology report · 2021Article
- A missense variant in NUF2, a component of the kinetochore NDC80 complex, causes impaired chromosome segregation and aneuploidy associated with microcephaly and short stature.Human genetics · 2021Article
- Unexpected expression of mismatch repair protein is more commonly seen with pathogenic missense than with other mutations in Lynch syndrome.Human pathology · 2020Article
- A Novel GermlineGenes · 2020Article
- Epithelioid variant of gastrointestinal stromal tumor harboring PDGFRA mutation and MLH1 gene alteration: A case report.Pathology international · 2019Article
- Biochemical and structural characterization of two variants of uncertain significance in the PMS2 gene.Human mutation · 2019Article
- A practical guide to biomarkers for the evaluation of colorectal cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Review
- Advances in Identification of Susceptibility Gene Defects of Hereditary Colorectal Cancer.Journal of Cancer · 2019Review
- Microsatellite instability test using peptide nucleic acid probe-mediated melting point analysis: a comparison study.BMC cancer · 2018Article
- Tumor Molecular Testing Guides Anti-PD-1 Therapy and Provides Evidence for Pathogenicity of Mismatch Repair Variants.The oncologist · 2018Article
- Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort.Oncotarget · 2017Article
- Molecular genetics of microsatellite-unstable colorectal cancer for pathologists.Diagnostic pathology · 2017Review
Corrections and comments
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Authors and funding
27 authors at 15 institutions in 4 countries.
Funding
Abstract
objectivesImmunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression.
designThis cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification).
resultsOf the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression.
conclusionsA substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified.
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