Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome

Eur J Hum Genet. 2009 Jul;17(7):919-27. doi: 10.1038/ejhg.2008.271. Epub 2009 Jan 21.


Microsatellite instability (MSI) is present in hereditary conditions due to mismatch repair (MMR) gene mutations. Following MSI analysis, tumor samples are classified into MSS (stable), MSI-L (low instability), and MSI-H (high instability) based on the fraction of unstable loci. Another MSI-based classification takes into account the size difference between mutant alleles in tumor DNA compared to wild-type alleles; two types of MSI, A and B, are recognized using this approach, type A being characterized by smaller, more subtle allelic shifts compared to type B. Biallelic mutations of MMR genes are associated with pediatric cancers, including glial tumors, in Turcot syndrome type 1 (TS1). However, most TS1-associated gliomas so far analyzed did not display MSI. We investigated the frequency of MSI in a series of 34 pediatric gliomas of different grade using a panel of five mononucleotide quasimonomorphic markers. Subtle qualitative changes were observed for the majority of markers in two glioblastomas (5.9% of the total series and 33.3% of glioblastomas). In both cases, family histories were compatible with TS1, and mutations of the PMS2 and MLH1 genes were identified. In one family, the MSI patterns were compared between the glioblastoma and a colon cancer from an affected relative, showing a clear qualitative difference, with the former displaying type A and the latter type B instability, respectively. These results were confirmed using additional microsatellite markers, indicating that knowledge of the association between TS1-related glial tumors and subtle type A MSI is important for full ascertainment of TS1 patients and appropriate counselling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / genetics*
  • Central Nervous System Neoplasms / genetics*
  • Child
  • Child, Preschool
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA / analysis
  • DNA Mismatch Repair / genetics
  • Female
  • Glioma / genetics*
  • Humans
  • Infant
  • Male
  • Microsatellite Instability*
  • Pedigree
  • Syndrome


  • Biomarkers, Tumor
  • DNA