Oncogene abnormalities in astrocytomas: EGF-R gene alone appears to be more frequently amplified and rearranged compared with other protooncogenes.
Ten astrocytomas were tested for gene amplification or rearrangement utilizing distinct probes to nine different oncogenes by Southern hybridization. The probes spanned the four major protein-coding classes of oncogenes; growth factor proteins (csis); growth factor receptor/tyrosine kinase-related proteins [erbB1 (epidermal growth factor receptor, EGF-R), neu (HER2/neu, erbB2), mos, yes]; nuclear binding proteins (c-myc, c-fos); and guanosine 5'-triphosphate binding proteins (N-ras, H-ras). Three astrocytomas, all glioblastomas, showed amplification of EGF-R-related sequences, and two of these amplifications were rearranged. Both rearrangements appeared similar by two different restriction endonucleases. Our findings suggest that it is primarily the EGF-R protooncogene (erbB1) that is amplified or rearranged in astrocytic neoplasms. No other oncogenes were amplified or rearranged, although EGF-R and neu cross-hybridization produced a "pseudo-rearranged" pattern for neu in EGF-R-amplified cases. The similar EGF-R restriction endonuclease abnormalities seen in two patients warrant further study.
Department of Pathology, College of Medicine, University of Iowa, Iowa City.
L J
LJ
Burgart
R A
RA
Robinson
S F
SF
Haddad
S A
SA
Moore
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics*; D015139:Blotting, Southern; D015342:DNA Probes; D004262:DNA Restriction Enzymes; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases
D015342:DNA Probes; D004262:DNA Restriction Enzymes; D066246:ErbB Receptors; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D020574:Proto-Oncogene Proteins c-sis; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; C501009:HRAS protein, human