AMPLIFICATION OF THE EPIDERMAL-GROWTH-FACTOR-RECEPTOR GENE CORRELATESWITH DIFFERENT GROWTH-BEHAVIOR IN HUMAN GLIOBLASTOMA

The objective of our study was to determine the frequency of EGF-recep tor-gene rearrangement in relation to tumour-growth behaviour in an un selected group of glioma patients. We investigated 73 glial tumours wi th different grades of malignancy (17 low-grade gliomas, 14 anaplastic variants, and 42 GBM) by Southern analysis, reverse transcriptase PCR (RT-PCR) amplification of mRNA, and Western analysis. An amplificatio n of the EGF-receptor gene was present in 19/42 GBM but in only 1 anap lastic astrocytoma. By RT-PCR, 4/19 GBM with gene amplification showed a specific amino-terminal aberrant splice mutation of 801 bp in addit ion to undeleted mRNA. By Western analysis, 27/42 GBM showed expressio n of the EGF-receptor protein. Protein levels, however, varied among i ndividual tumours. Four GBM containing an aberrant splice mutation exh ibited an immunoreactive protein of 130 kDa MW in addition to the norm al EGF-receptor protein p170. All GBM patients underwent surgery follo wed by a standard course of radiotherapy. Neuroradiological follow-up in 31/42 GBM patients consisted of bimonthly MRI examinations. There w as a statistically significant difference in the mean latency period u ntil tumour regrowth of patients suffering from GBM with and without E GF-receptor-gene amplification (9 weeks vs. 32 weeks). Our data indica te more rapid tumour regrowth kinetics of GBM with amplified EGF recep tor genes in vivo. (C) 1994 Wiley-Liss, Inc.