PTEN MUTATIONS IN GLIOMAS AND GLIONEURONAL TUMORS

Cytogenetic and loss of heterozygosity studies have suggested the pres ence of at least one tumor suppressor gene on chromosome 10 involved i n the formation of high grade gliomas, Recently, the PTEN gene, also t ermed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. In itial studies revealed mutations of PTEN in limited series of glioma c ell lines and glioblastomas. In order to systematically evaluate the i nvolvement 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 mere detected in 20/142 glioblast omas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic a strocytomas and 2/22 oligodendrogliomas, No PTEN mutations were detect ed 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 del etions of the PTEN gene; these were detected in 7 glioblastomas that d id not have PTEN mutations. Therefore, PTEN mutations occur in approxi mately 20% of glioblastomas but are rare in lower grade gliomas, These findings confirm that PTEN is one of the chromosome 10 tumor suppress or genes involved in the development of glioblastomas.