Amplification of the epidermal-growth-factor-receptor gene correlates with different growth behaviour in human glioblastoma.
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 1 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 MRI 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.
Schlegel
J
J
Institute of Neuropathology, University of Heidelberg, Germany.
Merdes
A
A
Stumm
G
G
Albert
F K
FK
Forsting
M
M
Hynes
N
N
Kiessling
M
M
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D005909:Glioblastoma / Q000235:genetics* / Q000503:physiopathology; D005910:Glioma / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
D066246:ErbB Receptors