title: Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.
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.
authors.affiliation: Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giunti
authors.forename: Valentina
authors.initials: V
authors.lastname: Cetica
authors.forename: Ugo
authors.initials: U
authors.lastname: Ricci
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giglio
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Elena
authors.initials: E
authors.lastname: Andreucci
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Sanzo
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Buccoliero
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Genitori
authors.forename: Maurizio
authors.initials: M
authors.lastname: Genuardi
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004247:DNA / Q000032:analysis; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D053842:Microsatellite Instability; D010375:Pedigree; D013577:Syndrome
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA