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

Planck, M LU ; Koul, A LU ; Fernebro, E LU ; Borg, A LU ; Kristoffersson, U LU ; Olsson, H LU ; Wenngren, E; Mangell, P LU and Nilbert, M LU (1999) In International Journal of Cancer 83(2). p.197-202
Abstract

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... (More)

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.

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published
subject
keywords
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
in
International Journal of Cancer
volume
83
issue
2
pages
6 pages
publisher
John Wiley & Sons
external identifiers
  • pmid:10471527
  • scopus:0032870177
ISSN
0020-7136
language
English
LU publication?
yes
id
f44be10d-a333-4ee8-bd99-2b50129274c5 (old id 1114434)
alternative location
http://www3.interscience.wiley.com/cgi-bin/fulltext/66500944/PDFSTART
date added to LUP
2008-07-04 11:04:26
date last changed
2017-01-01 04:39:00
@article{f44be10d-a333-4ee8-bd99-2b50129274c5,
  abstract     = {<p>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.</p>},
  author       = {Planck, M and Koul, A and Fernebro, E and Borg, A and Kristoffersson, U and Olsson, H and Wenngren, E and Mangell, P and Nilbert, M},
  issn         = {0020-7136},
  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},
  language     = {eng},
  month        = {10},
  number       = {2},
  pages        = {197--202},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {hMLH1, hMSH2 and hMSH6 mutations in hereditary non-polyposis colorectal cancer families from southern Sweden},
  volume       = {83},
  year         = {1999},
}