Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Detection of PMS2 Mutations by Screening Hereditary Nonpolyposis Colon Cancer Families from Denmark and Sweden

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Screening of three novel candidate genes in arrhythmogenic right ventricular cardiomyopathy

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Misclassification of allele CYP2C19*10 as CY2C19*2 by a commonly used PCR-RFLP procedure

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Exploring the hereditary background of renal cancer in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Background and Aims: Hereditary nonpolyposis colon cancer (HNPCC) and Lynch syndrome (LS) are characterized by defects in the mismatch repair (MMR) system, which protects the integrity of the genome. Pathogenic variants in four MMR genes (MLH1, MSH2, MSH6, and PMS2) are responsible for LS, an autosomal, dominant hereditary disease that occurs with a frequency of 2-5% among all colorectal cancer cases. It has been estimated that ∼2-5% of all pathogenic variants found in the four MMR genes in LS cases are detected in the PMS2 gene. An overview of detected variants is presented here. Materials and Methods: Long-range (LR) PMS2 polymerase chain reaction (PCR) and PMS2 multiplex ligation probe amplification (MLPA) assays were used to detect PMS2 variants in ∼1500 probands. In a subset of the probands, pathogenic PMS2 variants were detected by next-generation sequencing, and all detected variants were confirmed by LR-PCR combined with an MLPA assay. Results: A summary of PMS2 mutation analyses performed on colon cancer patients from molecular diagnostic laboratories in Denmark and Sweden is presented. By screening ∼1500 HNPCC probands, a total of 40 different PMS2 variants were detected in 71 probands (5%); 20 variants were classified as pathogenic (C5), 2 variants as likely pathogenic (C4), 15 variants as variants of unknown significance (VUSs) (C3), 1 variant as likely benign (C2), and 2 variants as benign (C1). In total, 22/71 (31%) of the probands carried a pathogenic sequence variant. Among the probands with isolated loss of pPMS2 expression, the fraction of pathogenic variants was 20/35 (55%). Conclusions: Approximately 5% of the probands found in the Danish and Swedish populations presented here carried a PMS2 variant. In this study, six novel pathogenic variants and seven VUSs are reported.

Original languageEnglish
JournalGenetic Testing and Molecular Biomarkers
Volume23
Issue number9
Pages (from-to)688-695
Number of pages8
ISSN1945-0265
DOIs
Publication statusPublished - Sep 2019

    Research areas

  • HNPCC, long-range PCR, Lynch syndrome, pathogenic variants, PMS2

ID: 57847607