The hPMS2 exon 5 mutation and malignant glioma

Patients with Turcot syndrome (TS) are predisposed to colon tumors and prim ary 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 glioblastoma s, 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 Ip. 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 ha d a unique histological appearance for TS. it was hypothesized that this ge netic defect may predispose to malignant gliomas with oligodendroglial feat ures. The authors therefore evaluated whether sporadic glioblastomas and ol igodendrogliomas undergo mutations of this region of the hPMS2 gene. Howeve r, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendr oglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial compone nt, the same genetic defect is nor commonly involved in sporadic oligodendr ogliomas or glioblastomas.