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

Maurizio Genuardi, Laura Giunti, Valentina Cetica, Ugo Ricci, Sabrina Giglio, Iacopo Sardi, Milena Paglierani, Elena Andreucci, Massimiliano Sanzo, Marco Forni, Anna Maria Buccoliero, Lorenzo Genitori

Risultato della ricerca: Contributo in rivistaArticolo in rivista

20 Citazioni (Scopus)

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. European Journal of Human Genetics (2009) 17, 919-927; doi:10.1038/ejhg.2008.271; published online 21 January 2009
Lingua originaleEnglish
pagine (da-a)919-927
Numero di pagine9
RivistaEuropean Journal of Human Genetics
Volume17
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • ADULT
  • CENTRAL-NERVOUS-SYSTEM
  • DEFICIENCY
  • DNA MISMATCH REPAIR
  • GENE PMS2
  • GERMLINE MUTATIONS
  • MONONUCLEOTIDE REPEATS
  • NONPOLYPOSIS COLORECTAL-CANCER
  • PMS2 MUTATIONS
  • TUMORS

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