Frameshift mutations at mononucleotide repeats in RAD50 recombinational DNA repair gene in colorectal cancers with microsatellite instability

Jpn J Cancer Res. 2001 Jun;92(6):587-91. doi: 10.1111/j.1349-7006.2001.tb01134.x.


To identify additional genes targeted for microsatellite instability (MSI), we search for human genes which contain mononucleotide repeats in their coding region, selected 7 genes (RAD50, DNA-PKcs, FLASH, Apaf-1, XPG, CtIP, and MLSN1), and analyzed frameshift mutations in them. Here we report that 60% (3 out of 5) of human colorectal cancer cell lines exhibiting a high frequency of MSI (MSI-H) and 46% (6 out of 13) of MSI-H primary colorectal tumors had mutations in the (A)9 repeat of RAD50 recombinational repair gene. In contrast, no frameshift mutations were found in any of the 5 MSI-negative colorectal cancer cell lines, 8 colorectal tumors exhibiting a low frequency of MSI (MSI-L), or 28 MSI-negative colorectal tumors. No mutations were found in the mononucleotide repeats of 6 other genes, even in MSI-H cancers. These results suggest that RAD50 frameshift mutations may play a role in the tumorigenesis of MSI-H colorectal cancers.

MeSH terms

  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA Repair
  • DNA-Binding Proteins*
  • Frameshift Mutation*
  • Fungal Proteins / genetics*
  • Humans
  • Microsatellite Repeats*
  • Mutation
  • Recombination, Genetic*
  • Repetitive Sequences, Nucleic Acid*
  • Saccharomyces cerevisiae Proteins*
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins