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2002
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| Acceso en liña: | https://doi.org/10.1002/ijc.10240 |
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| _version_ | 1866901098711744512 |
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| author | Caldes, T Godino, J de la Hoya, M García Carbonero, I Perez Segura, P Eng, C Benito, M Diaz Rubio, E |
| author_facet | Caldes, T Godino, J de la Hoya, M García Carbonero, I Perez Segura, P Eng, C Benito, M Diaz Rubio, E |
| contents | <p>HNPCC is an autosomal dominantly inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and endometrial cancer at a young age. It also entails an increased risk of a variety of other tumors, such as ovarian, gastric, uroepithelial and biliary tract cancers. The underlying pathogenic mutation lies in 1 of the 5 known DNA MMR genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We screened a total of 140 individuals from 56 Spanish families with suspected HNPCC for mutations in the DNA mismatch repair genes MLH1 and MSH2, using DGGE and direct DNA sequencing. Families were selected on the basis of a history of HNPCC-related tumors or the occurrence of other associated tumors in members besides the index case affected with colorectal cancer. We detected 14 definite pathogenic germline mutations, 9 in MLH1 and 5 in MSH2 in 13 unrelated families selected by the Amsterdam criteria and Bethesda guidelines (1 family carries 2 mutations) and 3 missense mutations in 3 unrelated families selected by the Amsterdam criteria. Among the 17 germline mutations noted in the Spanish cohort, 10 are novel, 7 in MLH1 and 3 in MSH2, perhaps demonstrating different mutational spectra in the Spanish population, where no founder mutation has been identified. Based on our results, we suggest that in the Spanish population not only HNPCC families fulfilling the Amsterdam criteria but also those following Bethesda guidelines should undergo genetic testing for MSH2 and MLH1 mutations.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_1002_ijc_10240 |
| institution | Zenodo |
| language | |
| publishDate | 2002 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Prevalence of germline mutations of MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer families from Spain Caldes, T Godino, J de la Hoya, M García Carbonero, I Perez Segura, P Eng, C Benito, M Diaz Rubio, E Adaptor Proteins, Signal Transducing Adult Age of Onset Carrier Proteins Colorectal Neoplasms, Hereditary Nonpolyposis DNA Mutational Analysis DNA, Neoplasm DNA-Binding Proteins female Germ-Line Mutation Humans Male Microsatellite Repeats Middle Aged MutL Protein Homolog 1 MutS Homolog 2 Protein Neoplasm Proteins Pedigree Polymerase Chain Reaction Proto-Oncogene Proteins Spain <p>HNPCC is an autosomal dominantly inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and endometrial cancer at a young age. It also entails an increased risk of a variety of other tumors, such as ovarian, gastric, uroepithelial and biliary tract cancers. The underlying pathogenic mutation lies in 1 of the 5 known DNA MMR genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We screened a total of 140 individuals from 56 Spanish families with suspected HNPCC for mutations in the DNA mismatch repair genes MLH1 and MSH2, using DGGE and direct DNA sequencing. Families were selected on the basis of a history of HNPCC-related tumors or the occurrence of other associated tumors in members besides the index case affected with colorectal cancer. We detected 14 definite pathogenic germline mutations, 9 in MLH1 and 5 in MSH2 in 13 unrelated families selected by the Amsterdam criteria and Bethesda guidelines (1 family carries 2 mutations) and 3 missense mutations in 3 unrelated families selected by the Amsterdam criteria. Among the 17 germline mutations noted in the Spanish cohort, 10 are novel, 7 in MLH1 and 3 in MSH2, perhaps demonstrating different mutational spectra in the Spanish population, where no founder mutation has been identified. Based on our results, we suggest that in the Spanish population not only HNPCC families fulfilling the Amsterdam criteria but also those following Bethesda guidelines should undergo genetic testing for MSH2 and MLH1 mutations.</p> |
| title | Prevalence of germline mutations of MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer families from Spain |
| topic | Adaptor Proteins, Signal Transducing Adult Age of Onset Carrier Proteins Colorectal Neoplasms, Hereditary Nonpolyposis DNA Mutational Analysis DNA, Neoplasm DNA-Binding Proteins female Germ-Line Mutation Humans Male Microsatellite Repeats Middle Aged MutL Protein Homolog 1 MutS Homolog 2 Protein Neoplasm Proteins Pedigree Polymerase Chain Reaction Proto-Oncogene Proteins Spain |
| url | https://doi.org/10.1002/ijc.10240 |