title: The hPMS2 exon 5 mutation and malignant glioma. Case report.
abstract: Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome 1p. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is not commonly involved in sporadic oligodendrogliomas or glioblastomas.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: M D
authors.initials: MD
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Perry
authors.forename: M C
authors.initials: MC
authors.lastname: Zlatescu
authors.forename: A O
authors.initials: AO
authors.lastname: Stemmer-Rachamimov
authors.forename: L C
authors.initials: LC
authors.lastname: Ang
authors.forename: Y
authors.initials: Y
authors.lastname: Ino
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: L E
authors.initials: LE
authors.lastname: Becker
authors.forename: D N
authors.initials: DN
authors.lastname: Louis
authors.forename: J G
authors.initials: JG
authors.lastname: Cairncross
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000251:Adenosine Triphosphatases; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D002675:Child, Preschool; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D005091:Exons; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D000070976:Mismatch Repair Endonuclease PMS2; D009363:Neoplasm Proteins / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics*; D010507:Periodicity; D016133:Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes