ONCOGENE AMPLIFICATION IN HUMAN GLIOMAS - A MOLECULAR CYTOGENETIC ANALYSIS

Nine cases of malignant gliomas were selected for the presence of doub le minutes (dmin) or homogeneously staining regions (hsr) detected by conventional cytogenetics. Analyses were performed on fresh (2 cases) or xenografted (5 cases) tumors or both (2 cases). A modified comparat ive genomic hybridization technique (mCGH) was applied exhibiting a si ngle amplified locus in 8 tumors and 4 amplified loci in one tumor. Re current sites of amplification were detected in 7p11-p12 (5 cases) and 1q32.1 (2 cases). Signals were also observed in 4q11-q12, 5p15.1, 7q3 1, 8q24.1 and 9p2 in one tumor each. Southern blotting demonstrated th at the genes for EGFR (epidermal growth factor receptor), PDGFRA (plat elet derived growth factor receptor alpha), MET and MYC oncogenes were involved in 7p11-p12, 4q11-q12, 7q31 and 8q24.1 amplifications, respe ctively. These amplifications were found by ill situ hybridization on tumor spreads, in dmin or episomes for EGFR, dmin for PDGFRA and MET, and hsr and dmin for MYC genes. Other mCGH signals, for which no targe t genes could be proposed, were confirmed by chromosome paintings on t umor metaphases. In one of the tumors, the coamplification of DNA from 5p15.1 and 9p2 bands in the same dmin was demonstrated.