hMLH1, hMSH2 and hMSH6 mutations in hereditary non-polyposis colorectal cancer families from southern Sweden
Författare
Summary, in English
We have screened 17 Southern Sweden individuals/families with suspected hereditary non-polyposis colorectal cancer (HNPCC) for mutations in the DNA-mismatch repair genes hMLH1, hMSH2 and hMSH6 using denaturing gradient gel electrophoresis, protein truncation test and direct DNA sequencing. The families were selected on the basis of a family history of HNPCC-related tumors or the occurrence of metachronous colorectal cancer/endometrial cancer at young age in an individual with a weak family history of cancer. Furthermore, we required that tumor tissue from at least one individual in the family had to display microsatellite instability. We identified germ-line mutations in 9 individuals from 8 families. Five families had mutations in hMLH1, 4 of which were splice site mutations, 2 had frameshift mutations in hMSH2 and 1 patient with metachronous endometrial and rectal cancer but with a weak family history of cancer had a nonsense mutation in hMSH6. Our results present novel germ-line DNA-repair gene mutations, one of these in hMSH6, and demonstrate the diversified mutation spectrum in Sweden, where no founder mutation has so far been identified.
Publiceringsår
1999-10-08
Språk
Engelska
Sidor
197-202
Publikation/Tidskrift/Serie
International Journal of Cancer
Volym
83
Issue
2
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
John Wiley & Sons Inc.
Ämne
- Cancer and Oncology
Nyckelord
- Adaptor Proteins, Signal Transducing
- Adult
- Base Pair Mismatch
- Carrier Proteins
- Colorectal Neoplasms, Hereditary Nonpolyposis
- DNA Mutational Analysis
- DNA Repair
- DNA-Binding Proteins
- Female
- Frameshift Mutation
- Genetic Testing
- Germ-Line Mutation
- Humans
- Male
- Middle Aged
- MutS Homolog 2 Protein
- Neoplasm Proteins
- Nuclear Proteins
- Proto-Oncogene Proteins
- Sweden
Status
Published
Forskningsgrupp
- Surgery
ISBN/ISSN/Övrigt
- ISSN: 0020-7136