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Genomic instability in neoplasia

R Honchel1, K C Halling, S N Thibodeau

  • 1Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, MN 55905, USA.

Seminars in Cell Biology
|February 1, 1995
PubMed
Summary

Microsatellite instability, a DNA alteration, is found in tumors from hereditary nonpolyposis colorectal cancer (HNPCC) and sporadic cancers. This points to DNA mismatch repair defects in tumorigenesis.

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Novel alterations in microsatellite DNA, known as microsatellite instability or replication error phenotype, are increasingly observed in tumors.
  • These alterations are present in hereditary nonpolyposis colorectal cancer (HNPCC), Muir-Torre syndrome (MTS), and a growing number of sporadic tumors.

Purpose of the Study:

  • To investigate the role of microsatellite instability in tumor development.
  • To identify genetic susceptibility loci associated with HNPCC and DNA mismatch repair.

Main Methods:

  • Analysis of microsatellite DNA alterations in tumor tissues.
  • Genetic linkage analysis to identify susceptibility loci.

Main Results:

  • Identification of four genetic susceptibility loci for HNPCC: hMSH2, hMLH1, hPMS1, and hPMS2.
  • These genes are involved in DNA mismatch repair.
  • Observed microsatellite instability in various tumor types, including HNPCC, MTS, and sporadic tumors.

Conclusions:

  • Defects in DNA mismatch repair are implicated in tumorigenesis.
  • Microsatellite instability may have significant implications for tumor mechanisms and clinical behavior.
  • Further research is needed to understand the significance of different microsatellite instability phenotypes.

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