Molecular and cytogenetic analysis of glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common primary tumor occurring in the central nervous system of adults. Although progress has been made in c linical management of this tumor, little is known about the molecular defec ts underlying the initiation and progression of GEM. To address these issue s, we have characterized five cases of GEM using cytogenetics, comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and direct sequencing. Ail Of these tumors were observed to have clonal chromo some aberrations. Complicated chromosome translocations including der(18)t( 2;4;12;18), der(X)t(X;10)(q27.1;p12.1) and der(10)t(10;15)(p11.23;q11.2), a nd der(1) (:1p31-->1q44:7q11.3-->7qter) were seen in three tumors. Loss of the CDKN2 gene was noted in four tumors. A gain of copy number of the Cathe psin L gene was seen in two tumors. Amplification of the CDK4, MDM2, and GL I/CHOP genes was noted in two tumors, and amplification of the PDGFR gene w as detected in one tumor. Mutation of exon 5 of the TP53 gene was found in three tumors. No mutation of the BCL10 gene was detected in five cases of G EM analyzed, although deletion of chromosome Ip was seen in two tumors. The se results provide information for further investigation of GEM. (C) 2000 E lsevier Science Inc. All rights reserved.