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Mutation in the mismatch repair gene Msh6 causes cancer susceptibility

W Edelmann1, K Yang, A Umar

  • 1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Cell
|December 9, 1997
PubMed

Insights

Mice lacking the MSH6 mismatch repair gene developed tumors and had shorter lifespans. This suggests MSH6 mutations contribute to cancer susceptibility, even without microsatellite instability.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • DNA mismatch repair (MMR) is crucial for genomic stability.
  • The MSH6 gene is a key component of the MMR system.
  • Defects in MMR genes are linked to various cancers.

Purpose of the Study:

  • To investigate the role of MSH6 in DNA repair and cancer development.
  • To characterize the phenotype of Msh6-deficient mice.

Main Methods:

  • Gene targeting was used to create Msh6-null mice.
  • Cellular extracts were assessed for mismatch repair activity.
  • Tumor development and microsatellite instability were analyzed in mutant mice.

Main Results:

  • Msh6-homozygous cells showed defective repair of single nucleotide mismatches.
  • Msh6-deficient mice had reduced lifespans and developed various tumors, including gastrointestinal tumors and lymphomas.
  • Tumors in these mice did not exhibit microsatellite instability.

Conclusions:

  • MSH6 is essential for repairing single nucleotide mismatches.
  • MSH6 mutations confer cancer susceptibility.
  • Germline MSH6 mutations may be associated with a cancer predisposition syndrome independent of microsatellite instability.

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