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http://purl.uniprot.org/citations/16472587http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16472587http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16472587http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

The role of the mismatch repair gene PMS2 in hereditary nonpolyposis colorectal carcinoma (HNPCC) is not fully clarified. To date, only 7 different heterozygous truncating PMS2 mutations have been reported in HNPCC-suspected families. Our aim was to further assess the role of PMS2 in HNPCC.

Methods

We performed Southern blot analysis in 112 patients from MLH1-, MSH2-, and MSH6-negative HNPCC-like families. A subgroup (n = 38) of these patients was analyzed by denaturing gradient gel electrophoresis (DGGE). In a second study group consisting of 775 index patients with familial colorectal cancer, we performed immunohistochemistry using antibodies against MLH1, MSH2, MSH6, and PMS2 proteins. In 8 of 775 tumors, only loss of PMS2 expression was found. In these cases, we performed Southern blot analysis and DGGE. Segregation analysis was performed in the families with a (possibly) deleterious mutation.

Results

Seven novel mutations were identified: 4 genomic rearrangements and 3 truncating point mutations. Three of these 7 families fulfill the Amsterdam II criteria. The pattern of inheritance is autosomal dominant with a milder phenotype compared with families with pathogenic MLH1 or MSH2 mutations. Microsatellite instability and immunohistochemical analysis performed in HNPCC-related tumors from proven carriers showed a microsatellite instability high phenotype and loss of PMS2 protein expression in all tumors.

Conclusions

We show that heterozygous truncating mutations in PMS2 do play a role in a small subset of HNPCC-like families. PMS2 mutation analysis is indicated in patients diagnosed with a colorectal tumor with absent staining for the PMS2 protein."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2005.10.052"xsd:string
http://purl.uniprot.org/citations/16472587http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2005.10.052"xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Wagner A."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Wagner A."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Gomez E."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Gomez E."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Wijnen J.T."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Wijnen J.T."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"van der Klift H.M."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"van der Klift H.M."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Breuning M.H."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Breuning M.H."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Morreau H."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Morreau H."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Ausems M.G."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Ausems M.G."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"van Puijenbroek M."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"van Puijenbroek M."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Jagmohan-Changur S."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Jagmohan-Changur S."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Tops C."xsd:string
http://purl.uniprot.org/citations/16472587http://purl.uniprot.org/core/author"Tops C."xsd:string
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