title: PTEN mutations in gliomas and glioneuronal tumors.
abstract: Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas. These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Germany.
authors.forename: E M
authors.initials: EM
authors.lastname: Duerr
authors.forename: B
authors.initials: B
authors.lastname: Rollbrocker
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: N
authors.initials: N
authors.lastname: Peters
authors.forename: B
authors.initials: B
authors.lastname: Meyer-Puttlitz
authors.forename: D N
authors.initials: DN
authors.lastname: Louis
authors.forename: J
authors.initials: J
authors.lastname: Schramm
authors.forename: O D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: R
authors.initials: R
authors.lastname: Parsons
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D005910:Glioma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D017354:Point Mutation / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human