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hMLH1, hMSH2 and hMSH6 mutations in hereditary non‐polyposis colorectal cancer families from Southern Sweden
Author(s) -
Planck Maria,
Koul Anjila,
Fernebro Eva,
Borg Åke,
Kristoffersson Ulf,
Olsson Håkan,
Wenngren Eva,
Mangell Peter,
Nilbert Mef
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991008)83:2<197::aid-ijc9>3.0.co;2-x
Subject(s) - frameshift mutation , germline mutation , microsatellite instability , genetics , dna mismatch repair , cancer , mutation , family history , nonsense mutation , colorectal cancer , biology , lynch syndrome , medicine , cancer research , microsatellite , gene , missense mutation , allele
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. Int. J. Cancer 83:197–202, 1999. © 1999 Wiley‐Liss, Inc.