AMPLIFICATION OF MULTIPLE GENES FROM CHROMOSOMAL REGION 12Q13-14 IN HUMAN-MALIGNANT GLIOMAS - PRELIMINARY MAPPING OF THE AMPLICONS SHOWS PREFERENTIAL INVOLVEMENT OF CDK4, SAS, AND MDM2

We have investigated 234 tumors of the central nervous system for ampl ification of 9 different loci from 12q13 14 and report that about 15% of the anaplastic astrocytomas and glioblastomas show amplification at this chromosomal region. The genes most frequently amplified were CDK 4 and SAS (18 of 19 cases). MDM2 was coamplified with CDK4 and SAS in 11 tumors while one glioblastoma showed only MDM2 amplification. Some amplicons additionally included GADD153 (9 cases), GLI (6 cases), A2MR (3 cases), and the anonymous locus D12S8 (2 cases). Either MDM2 or CD K4 and SAS showed the highest amplification level in each individual a mplicon and amplification of these genes was consistently accompanied by strong overexpression. Our results thus suggest CDK4, SAS, and MDM2 as main targets for the amplification; however, the possibility exist s that all amplicons share a common amplified region between MDM2 and CDK4/SAS which might contain one or more as yet unidentified genes.