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Loci Associated with Malignant Progression in Astrocytomas: A Candidate on Chromosome 19q¹

Institut für Neuropathologie, Universitätskliniken Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany [A. v. D., B. B., R. J., A. W., J. K., S. A., R. W., F. F., J. N., O. D. W.]; Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524 [A. G. M.]; Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02129 [D. N. L.]; Neurochirurgische Klinik Köln-Merheim, D-51109 Germany [D. L.]; and Neurochirurgische Universitätsklinik Bonn, D-53105 Germany [J. S.]

WHO grades II and III astrocytomas frequently exhibit loss of genetic material on chromosomes 9p, 11p, 17p, 19q, and 22q, indicating that these chromosomal regions harbor tumor suppressor genes involved in the pathogenesis of astrocytic neoplasms. The present study was conducted to examine whether these genetic regions are involved in the process of malignant progression from astrocytoma WHO grade II (A II) to anaplastic astrocytoma WHO grade III (A III). We have analyzed 44 astrocytomas, i.e., 18 A II and 26 A III for loss of heterozygosity (LOH) on chromosomes 1p, 1q, 9p, 9q, 10p, 10q, 11p, 13q, 17p, 19p, 19q, and 22q and for amplification of the epidermal growth factor receptor gene. A polymerase chain reaction-based assay with microsatellite repeat sequences was used for the detection of polymorphisms on silver-stained polyacrylamide gels. LOH on 9p was seen in 1 of 18 (6%) informative cases of A II and 4 of 24 (17%) informative cases of A III. LOH on 17p was observed in 9 of 17 (53%) informative cases of A II and 15 of 26 (58%) informative cases of A III. LOH on 19q was detected in 2 of 18 (11%) informative cases of A II and in 12 of 26 (46%) informative cases of A III. The association of LOH on 19q with anaplasia in astrocytoma was significant (P = 0.015). Amplification of the epidermal growth factor receptor gene was not detected in A II or A III. These data suggest that a putative tumor suppressor gene on the long arm of chromosome 19 is a candidate for a gene associated with tumor progression in astrocytic gliomas.

¹ This work is supported by the Deutsche Forschungsgemeinschaft, the University of Bonn, and the state of Nordrhein-Westfalen. S. A. is the recipient of a scholarship from the Alexander von Humboldt Foundation.

² To whom requests for reprints should be addressed.

Received 10/27/93. Accepted 2/ 4/94.

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