Somatic mutations in the hMSH2 gene in microsatellite unstable colorectal carcinomas
| Autor: | Ragnhild A. Lothe, Lipford J, Michael F. Kane, Sigrid Lystad, Torleiv O. Rognum, Anne Lise Børresen, Gunn Iren Meling, Paul T. Morrison, Richard D. Kolodner |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
DNA Repair Somatic cell Molecular Sequence Data DNA Satellite Biology medicine.disease_cause Germline Fungal Proteins Germline mutation Genetics medicine Humans Amino Acid Sequence Molecular Biology Gene Germ-Line Mutation Genetics (clinical) Aged Aged 80 and over Mutation Polymorphism Genetic Base Sequence Microsatellite instability DNA Neoplasm General Medicine Middle Aged medicine.disease DNA-Binding Proteins MutS Homolog 2 Protein Cancer research Microsatellite DNA mismatch repair Colorectal Neoplasms |
| Zdroj: | Human Molecular Genetics. 4:2065-2072 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/4.11.2065 |
| Popis: | Microsatellite instability is frequently seen in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Germline mutations in the mismatch repair gene hMSH2 account for approximately 50% of these cases. Tumors from sporadic cases also exhibit this microsatellite instability phenotype, although at a lower frequency, and very few somatically derived mutations have so far been reported in such tumors. In this study DNA from 23 primary colorectal carcinomas (four familial and 19 sporadic cases) exhibiting microsatellite instability were screened for mutations in the hMSH2 gene using constant denaturant gel electrophoresis (CDGE). Among the sporadic cases, five (26%) were found to have somatically derived mutations. One tumor revealed two different mutations, possibly leading to a homozygous inactivation of the gene. One of the four familial cases was classified as having HNPCC, and a germline as well as a somatic mutation were found in this tumor. These results demonstrate that a considerable proportion of sporadic colorectal cancers with microsatellite instability, have somatic mutations in the hMSH2 gene. |
| Databáze: | OpenAIRE |
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