hMLH1, hMSH2 and hMSH6 mutations in hereditary non-polyposis colorectal cancer families from Southern Sweden

✍ Scribed by Maria Planck; Anjila Koul; Eva Fernebro; Åke Borg; Ulf Kristoffersson; Håkan Olsson; Eva Wenngren; Peter Mangell; Mef Nilbert

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 101 KB
• Volume: 83
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19991008)83:2<197::aid-ijc9>3.0.co;2-x

✦ Synopsis

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.