The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.

På svenska

Author

Summary, in English

The majority of tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread microsatellite instability (MSI) and somatic mutations in repeated sequences in several cancer-associated genes. An inverse relationship between MSI and chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors are generally characterized by diploid or near-diploid cells with few or no chromosomal rearrangements. We have studied MSI, somatic mutations in repeat-containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a patient with a germline MLH1 mutation. Mutations in coding repeats were assessed in 10 macroscopically separate areas of the primary tumor and in two lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4, and TGFBRII) showed a consistent lack of mutations, whereas others (BAX, Caspase-5 and IGFIIR) displayed alterations in some tumor regions but not in others. The tumor had DNA-index 1.1-1.2 and a stable, aberrant karyotype with extra copies of chromosomes 7 and 12 and the structural aberrations i(1q), der(20)t(8;20), and der(22)t(1;22). The finding of CIN, MSI, and somatic mutations in coding repeats in this tumor suggests that these phenomena may act together in HNPCC tumorigenesis. Furthermore, the observed intratumoral heterogeneity of mutations in coding repeats implies these changes occur late in tumorigenesis and, thus, probably play a role in tumor progression rather than initiation.

Publishing year

2002

Language

English

Pages

46-54

Publication/Series

Cancer Genetics and Cytogenetics

Volume

134

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Cancer and Oncology

Keywords

  • DNA Mutational Analysis
  • Neoplasm : chemistry
  • DNA
  • Neoplasm : genetics
  • Female
  • Flow Cytometry
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease : genetics
  • Human
  • In Situ Hybridization
  • Fluorescence
  • Karyotyping
  • Microsatellite Repeats
  • Mutation
  • Neoplasm Proteins : genetics
  • Nucleic Acid : genetics
  • Repetitive Sequences
  • Ploidies
  • Support
  • Non-U.S. Gov't
  • Hereditary Nonpolyposis : pathology
  • Colorectal Neoplasms
  • Hereditary Nonpolyposis : genetics
  • Colonic Neoplasms : pathology
  • Colonic Neoplasms : genetics
  • Chromosome Aberrations

Status

Published

Research group

  • Surgery

ISBN/ISSN/Other

  • ISSN: 0165-4608