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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

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

Publication and Content Type

art (subject category)

ref (subject category)