ArticleFamilial cancer2020
Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics.
Article in Familial cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Mapping the Prevalence of Lynch Syndrome in the Ceará-Northeast of Brazil.Clinical genetics · 2026Article
- Population frequency of Predicted pathogenic MisMatch Repair (MMR) gene variants in Lynch syndrome from bioinformatic analyses of the general population.Scientific reports · 2025Article
- Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.Clinical epigenetics · 2024Article
- The impact of inversions across 33,924 families with rare disease from a national genome sequencing project.American journal of human genetics · 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
- Detecting inversions in routine molecular diagnosis in MMR genes.Familial cancer · 2022Article
- Application of targeted nanopore sequencing for the screening and determination of structural variants in patients with Lynch syndrome.Journal of human genetics · 2021Article
- 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
- Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders.Cells · 2021Review
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Should All Individuals Be Screened for Genetic Predisposition to Cancer?Genetics research · 2021Review
- Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.Cancers · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Routine diagnostics for colorectal cancer patients suspected of having Lynch-Syndrome (LS) currently uses Next-Generation-Sequencing (NGS) of targeted regions within the DNA mismatch repair (MMR) genes. This analysis can reliably detect nucleotide alterations and copy-number variations (CNVs); however, CNV-neutral rearrangements comprising gene inversions or large intronic insertions remain undetected because their breakpoints are usually not covered. As several founder mutations exist for LS, we established PCR-based screening methods for five known rearrangements in MLH1, MSH2, or PMS2, and investigated their prevalence in 98 German patients with suspicion of LS without a causative germline variant or CNV detectable in the four MMR genes. We found no recurrence of CNV-neutral structural rearrangements previously described: Neither for two inversions in MLH1 (exon 1 and exon 16-19) within 33 MLH1-deficient patients, nor for two inversions in MSH2 (exon 1-7 and exon 2-6) within 48 MSH2-deficient patients. The PMS2 insertion in intron 7 was detected in one of 17 PMS2-deficient patients. None of the four genomic inversions constitutes a founder event within the German population, but we advise to test the rare cases with unsolved PMS2-deficiency upon the known insertion. As a next diagnostic step, tumour tissue of the unsolved patients should be sequenced for somatic variants, and germline analysis of additional genes with an overlapping clinical phenotype should be considered. Alternatively, full-length cDNA analyses may detect concealed MMR-defects in cases with family history.
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