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Somatic frameshift alterations in mononucleotide repeat-containing genes in different tumor types from an HNPCC family with germline MSH2 mutation

  • M Planck
  • E Wenngren
  • Åke Borg
  • Håkan Olsson
  • M Nilbert
Publishing year: 2000-09
Language: English
Pages: 33-39
Publication/Series: Genes, Chromosomes and Cancer
Volume: 29
Issue: 1
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a germline mutation in one of several DNA repair genes, which in the tumors is reflected as microsatellite instability (MSI). MSI+ tumors have been found to carry somatic frameshift mutations in mononucleotide repeats within the coding regions of several genes involved in growth control, apoptosis, and DNA repair, e.g., TGFBRII, BAX, IGFIIR, TCF4, MSH3, and MSH6. We have studied the occurrence of somatic frameshift alterations in these mononucleotide repeat-containing genes in 24 tumors (15 colorectal cancers, 1 colon adenoma, 4 endometrial cancers, 1 ovarian cancer, 1 gastric cancer, 1 urothelial cancer, and 1 duodenal cancer) from 14 individuals in an HNPCC family with germline hMSH2 mutation. Such somatic frameshift mutations occurred at a variable frequency; the long mononucleotide repeats that characterize intronic MSI markers were mutated in the majority of tumors, 13 of the tumors displayed alterations in the (A)(10) tract of TGFBII, eight tumors (all of gastrointestinal origin) had alterations in the (A)(9) repeat of TCF4, and one to five tumors had somatic frameshift alterations in the shorter mononucleotide repeats of IGFIIR, BAX, MSH3, and MSH6. Thus, longer mononucleotide repeats were more frequently affected by somatic frameshift mutations. The pattern of alterations varied between the tumors from different family members as well as between different tumors from the same individual. To what extent this variable pattern depends on the widespread mismatch repair deficiency induced by the underlying MSH2 mutation, or represents alternative ways whereby the tumors can achieve a tumorigenic phenotype, is unknown. We suggest, however, that the accumulation of somatic frameshifts, rather than the specific loci in which these occur, drives the development of the tumorigenic phenotype in HNPCC.


  • Cancer and Oncology
  • Aged
  • Colorectal Neoplasms
  • Colorectal Neoplasms, Hereditary Nonpolyposis
  • DNA-Binding Proteins
  • Female
  • Frameshift Mutation
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • MutS Homolog 2 Protein
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins
  • Sequence Analysis, DNA
  • Trinucleotide Repeat Expansion


  • Lund Melanoma Study Group
  • ISSN: 1045-2257
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2


Project manager

Familial Breast Cancer



Oncology and Pathology, MV

MV 404 C21C2