Amplification of the epidermal‐growth‐factor‐receptor gene correlates with different growth behaviour in human glioblastoma

Abstract

The objective of our study was to determine the frequency of EGF‐receptor‐gene rearrangement in relation to tumour‐growth behaviour in an unselected group of glioma patients. We investigated 73 glial tumours with 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 amplification of the EGF‐receptor gene was present in 19/42 GBM but in only I anaplastic astrocytoma. By RT‐PCR, 4/19 GBM with gene amplification showed a specific amino‐terminal aberrant splice mutation of 801 bp in addition to undeleted mRNA. By Western analysis, 27/42 GBM showed expression of the EGF‐receptor protein. Protein levels, however, varied among individual tumours. Four GBM containing an aberrant splice mutation exhibited an immunoreactive protein of 130 kDa MW in addition to the normal EGF‐receptor protein p170. All GBM patients underwent surgery followed by a standard course of radiotherapy. Neuroradiological follow‐up in 31/42 GBM patients consisted of bimonthly MRJ examinations. There was a statistically significant difference in the mean latency period until tumour regrowth of patients suffering from GBM with and without EGF‐receptor‐gene amplification (9 weeks vs. 32 weeks). Our data indicate more rapid tumour regrowth kinetics of GBM with amplified EGF receptor genes in vivo.