ArticleFamilial cancer2014
Inversion of exons 1-7 of the MSH2 gene is a frequent cause of unexplained Lynch syndrome in one local population.
Article in Familial cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Unexplained mismatch repair deficiency: Case closed.HGG advances · 2023Pooled it
- The germline MLH1 c.2054 C>T mutation disrupts DNA mismatch repair and is detectable by digital PCR.Cancer letters · 2026Article
- Lynch Syndrome in Focus: A Multidisciplinary Review of Cancer Risk, Clinical Management, and Special Populations.Cancers · 2025Review
- The impact of inversions across 33,924 families with rare disease from a national genome sequencing project.American journal of human genetics · 2024Article
- Functional and phenotypic consequences of an unusual inversion in MSH2.Familial cancer · 2024Article
- Genome sequencing identifies complex structural MLH1 variant in unsolved Lynch syndrome.Molecular genetics & genomic medicine · 2023Article
- A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.Journal of translational medicine · 2023Article
- 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
- The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes.Research (Washington, D.C.) · 2023Article
- Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome.Genome biology · 2022Article
- Detecting inversions in routine molecular diagnosis in MMR genes.Familial cancer · 2022Article
- Article
- Review
- Genetic testing for inherited colorectal cancer and polyposis, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome.Genes, chromosomes & cancer · 2021Article
- Prevalence of cancer susceptibility variants in patients with multiple Lynch syndrome related cancers.Scientific reports · 2021Article
- Germline and Tumor Sequencing as a Diagnostic Tool To Resolve Suspected Lynch Syndrome.The Journal of molecular diagnostics : JMD · 2021Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Correlation of MSH2 exonic deletions and protein downregulation with breast cancer biomarkers and outcome in Pakistani women/patients.Environmental science and pollution research international · 2021Article
- Germline Structural Variations in Cancer Predisposition Genes.Frontiers in genetics · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Germline mutations in DNA mismatch repair (MMR) genes, such as MSH2, cause Lynch syndrome, an autosomal dominant predisposition to colorectal as well as other cancers. Our research clinic focuses on hereditary colorectal cancer, and over the past 9 years we have identified germline mutations in DNA MMR genes in 101 patients using commercial genetic reference laboratories. We also collected samples from twelve patients with absent MSH2 protein expression and microsatellite instability in tumor tissue, with a family history suggestive of Lynch syndrome, but negative germline test results. The most likely explanation for this set of results is that the germline testing did not detect true germline mutations in these patients. Two of our patients with failed commercial testing were later found to have deletions in the 3' region of EPCAM, the gene just upstream of MSH2, but no explanation could be found for inactivation of MSH2 in the other ten patients. We used allelic dropout in long PCR to look for potential regions of rearrangement in the MSH2 gene. This method detected a potential rearrangement breakpoint in the same region of MSH2 where one breakpoint of a 10 Mb inversion was reported previously. We tested these ten patients for this inversion. Six of 10 patients had the inversion, indicating the importance of including testing for this inversion in patients suspected of having MSH2-type Lynch syndrome in our population. Additionally, this method could be further developed to look for inversions in other genes where current methods of testing fail to find a causative mutation.
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