PMS2 Involvement in Patients Suspected of Lynch Syndrome

Renee C. Niessen, Jan H. Kleibeuker, Helga Westers, Paul O. J. Jager, Dennie Rozeveld, Krista K. Bos, Wytske Boersma-van Ek, Harry Hollema, Rolf H. Sijmons, Robert M. W. Hofstra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

Abstract

It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene, PMS2, play a far more important role in Lynch syndrome than initially thought. To explore this further, we determined the prevalence of pathogenic germline PMS2 mutations in a series of Lynch syndrome-suspected patients. Ninety-seven patients who had early-onset microsatellite instable colorectal or endometrial cancer, or multiple Lynch syndrome-associated tumors and/or were from an Amsterdam Criteria II-positive family were selected for this study. These patients carried no pathogenic germline mutation in MLH1, MSH2, or MSH6. When available, tumors were investigated for immunohistochemical staining (IHC) for PMS2. PMS2 was screened in all patients by exon-by-exon sequencing. We identified four patients with a pathogenic PMS2 mutation (4%) among the 97 patients we selected. IHC of PMS2 was informative in one of the mutation carriers, and in this case, the tumor showed loss of PMS2 expression. In conclusion, our study confirms the finding of previous studies that PMS2 is more frequently involved in Lynch syndrome than originally expected. (C) 2009 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)322-329
Number of pages8
JournalGENES CHROMOSOMES & CANCER
Volume48
Issue number4
DOIs
Publication statusPublished - Apr-2009

Keywords

  • NONPOLYPOSIS COLORECTAL-CANCER
  • DNA MISMATCH-REPAIR
  • MICROSATELLITE INSTABILITY
  • MUTATION ANALYSIS
  • COLON-CANCER
  • GENE
  • IDENTIFICATION
  • CARRIERS
  • HNPCC
  • MSH6

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