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PMS2 involvement in patients suspected of Lynch syndrome.
- Source :
-
Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2009 Apr; Vol. 48 (4), pp. 322-9. - Publication Year :
- 2009
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing metabolism
Adenocarcinoma pathology
Adenosine Triphosphatases metabolism
Colon metabolism
Colon pathology
Colonic Neoplasms pathology
Colorectal Neoplasms, Hereditary Nonpolyposis metabolism
Colorectal Neoplasms, Hereditary Nonpolyposis pathology
DNA Methylation
DNA Mutational Analysis
DNA Repair Enzymes metabolism
DNA-Binding Proteins metabolism
Humans
Immunohistochemistry
Microsatellite Instability
Mismatch Repair Endonuclease PMS2
MutL Protein Homolog 1
Nuclear Proteins genetics
Nuclear Proteins metabolism
Adenosine Triphosphatases genetics
Colorectal Neoplasms, Hereditary Nonpolyposis genetics
DNA Repair Enzymes genetics
DNA-Binding Proteins genetics
Germ-Line Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2264
- Volume :
- 48
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Genes, chromosomes & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 19132747
- Full Text :
- https://doi.org/10.1002/gcc.20642