Use of mononucleotide repeat markers for detection of microsatellite instability in mouse tumors

Mol Carcinog. 2005 Dec;44(4):285-92. doi: 10.1002/mc.20146.

Abstract

Tumors lacking DNA mismatch repair activity (MMR) from patients with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or those with sporadic colorectal cancer can be identified by the presence of high levels of instability in repetitive sequences known as microsatellites (MSI). The assessment of MSI phenotype in human tumors helps to establish a clinical diagnosis and is accomplished with a reference panel of five mononucleotide repeats. By contrast, detection of MSI in mouse tumors has proven to be problematic and lack of a uniform set of markers for classification of MSI has impeded comparison of results between studies. We tested for MSI in intestinal tumors from MMR-deficient mice with four mononucleotide repeats with polyA(24-37) tracts and three new markers with extended polyA(59-67) tracts. All seven markers were sensitive to MSI in MMR-deficient tumors, but those with extended mononucleotide tracts displayed larger deletions, which were easily distinguishable from the germline alleles. With a panel of the five most sensitive and specific mononucleotide repeats, a high level of MSI was detected in 100% of MMR-deficient tumors, but not in tumors with MMR activity. This novel panel is an improvement over existing combinations of mono- and dinucleotide repeat markers and should facilitate MSI screening and standardize results from different studies.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Pair Mismatch / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Genes, APC / physiology
  • Genomic Instability*
  • Intestinal Neoplasms / diagnosis*
  • Intestinal Neoplasms / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microsatellite Repeats / genetics*
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics
  • MutS Homolog 2 Protein / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Repetitive Sequences, Nucleic Acid*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Mlh1 protein, mouse
  • Nuclear Proteins
  • Msh2 protein, mouse
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein