Prevalence of germline mutations ofMLH1 andMSH2 in hereditary nonpolyposis colorectal cancer families from Spain
| Autor: | Javier Godino, Iciar Garcia Carbonero, Trinidad Caldés, Charis Eng, Manuel Benito, Eduardo Díaz-Rubio, Miguel de la Hoya, Pedro Pérez Segura |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Cancer Research Amsterdam criteria DNA Mutational Analysis Biology MLH1 medicine.disease_cause Polymerase Chain Reaction Germline mutation Proto-Oncogene Proteins medicine PMS2 Humans Age of Onset neoplasms Germ-Line Mutation Adaptor Proteins Signal Transducing Genetic testing Genetics Mutation medicine.diagnostic_test Nuclear Proteins nutritional and metabolic diseases DNA Neoplasm Middle Aged Colorectal Neoplasms Hereditary Nonpolyposis digestive system diseases Neoplasm Proteins Pedigree DNA-Binding Proteins MSH6 MutS Homolog 2 Protein Oncology Spain MSH2 Female Carrier Proteins MutL Protein Homolog 1 Microsatellite Repeats |
| Zdroj: | International Journal of Cancer. 98:774-779 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.10240 |
| Popis: | 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. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text