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- Title
Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.
- Authors
Giunti, Laura; Cetica, Valentina; Ricci, Ugo; Giglio, Sabrina; Sardi, Iacopo; Paglierani, Milena; Andreucci, Elena; Sanzo, Massimiliano; Forni, Marco; Buccoliero, Anna Maria; Genitori, Lorenzo; Genuardi, Maurizio
- Abstract
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
European journal of human genetics : EJHG, 2009, Vol 17, Issue 7, p919
- ISSN
1476-5438
- Publication type
Journal Article
- DOI
10.1038/ejhg.2008.271