Coamplification of simple repetitive DNA fingerprint fragments and the EGFR gene in human gliomas.
DNA fingerprints were generated by the oligonucleotide probe (GTG)5 from surgically removed tissue and/or primary cell culture of 36 intracranial tumors (31 gliomas, 1 medulloblastoma, 4 metastatic carcinomas) and compared with the constitutional banding pattern obtained from the peripheral blood leukocytes of each patient. A multitude of somatic changes was detected and found to reflect the chromosome alterations identified by parallel karyotype analysis. Gain and/or loss of bands or significant band intensity shifts could be demonstrated in the fingerprints of more than 80% of the tumors investigated. This included a highly amplified fingerprint fragment in five independent gliomas (four of them had double minutes, dmin) which appeared not individual- but tumor-specific (2.4 kilobases, kb, after HaeIII digestion). Rehybridization with the oligonucleotide probes (GT)8 and (GATA)4, respectively, revealed additional amplified fingerprint fragments in the tumor DNA of these patients. While a (ca/gt)n fragment (2.6 kb. HaeIII) was also found to be amplified in all five cases, one band detected with (GATA)4 (1.4 kb, HaeIII) represented a unique feature for one of these tumors only. Amplification of the epidermal growth factor receptor (EGFR) gene via Southern blot hybridization was revealed only in those tumors showing the amplified DNA fingerprint fragments as well. Thus in many gliomas the amplification unit harbors two simple repetitive DNA fingerprint loci, (cac/gtg)n and (ca/gt)n, in addition to the EGFR gene.
Nürnberg
P
P
Institut für Medizinische Genetik des Bereiches Medizin (Charité) der Humboldt-Universität zu Berlin, Federal Republic of Germany.
Zischler
H
H
Fuhrmann
E
E
Thiel
G
G
Losanova
T
T
Kinzel
D
D
Nisch
G
G
Witkowski
R
R
Epplen
J T
JT
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000556:secondary; D002277:Carcinoma / Q000235:genetics / Q000556:secondary; D002648:Child; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000648:ultrastructure; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005784:Gene Amplification; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D066246:ErbB Receptors