PMS2 Involvement in Patients Suspected of Lynch Syndrome
| Autor: | Wytske Boersma-van Ek, Paul O. J. Jager, Jan H. Kleibeuker, Helga Westers, Harry Hollema, Renee C. Niessen, Krista K. Bos, Rolf H. Sijmons, Robert M.W. Hofstra, Dennie Rozeveld |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Amsterdam criteria congenital hereditary and neonatal diseases and abnormalities DNA MISMATCH-REPAIR Colon MICROSATELLITE INSTABILITY DNA Mutational Analysis MUTATION ANALYSIS HNPCC Biology Adenocarcinoma MLH1 Germline mutation Genetics PMS2 medicine Humans neoplasms Germ-Line Mutation Adaptor Proteins Signal Transducing Mismatch Repair Endonuclease PMS2 Adenosine Triphosphatases IDENTIFICATION COLON-CANCER Microsatellite instability Nuclear Proteins nutritional and metabolic diseases NONPOLYPOSIS COLORECTAL-CANCER DNA Methylation MSH6 medicine.disease CARRIERS Colorectal Neoplasms Hereditary Nonpolyposis Immunohistochemistry GENE Lynch syndrome digestive system diseases DNA-Binding Proteins DNA Repair Enzymes MSH2 Colonic Neoplasms Cancer research MutL Protein Homolog 1 |
| Zdroj: | GENES CHROMOSOMES & CANCER, 48(4), 322-329. Wiley |
| ISSN: | 1045-2257 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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