CHROMOSOMAL CHANGES AND CORRESPONDINGLY ALTERED PROTOONCOGENE EXPRESSION IN HUMAN GLIOMAS - VALUE OF COMBINED CYTOGENETIC AND MOLECULAR GENETIC-ANALYSIS

A combined cytogenetic and molecular genetic study was performed to an alyze seven primary brain tumors: one oligoastrocytoma WHO-grade II, o ne anaplastic astrocytoma grade III, one anaplastic astrocytoma grade III/IV and four glioblastomas by G-banding and RNA dot blotting. A nor mal karyotype was found in the oligoastrocytoma. One of the two anapla stic astrocytomas (male) contained cells with a normal karyotype and c ells with a Y-chromosomal loss, and the other one showed structural ab normalities too complex for complete analysis. in mostly polyploid cel ls. Two of the four glioblastomas had few and the other two multiple c hromosomal changes such as + 7, +20, -8, -9 del(9)(p21), -10, del(10) (q24), -13,14, del(17)(p21), -22, add(3)(q13), double minutes and mark er chromosomes. Compared to normal brain, all tumors had an increased EGFr and both anaplastic astrocytomas as well as three glioblastomas a decreased H-ras expression. The two glioblastomas with multiple chrom osomal changes showed increased EGFr, Ki-ras, myb, mos and myc, decrea sed H-ras and N-ras and unchanged levels of abl, src and sis. Both the cytogenetic and molecular genetic findings are compatible even in the case of chromosomal losses, where the genes on the remaining allele m ay be responsible for dominant gene regulation mechanisms which result in a protooncogene overexpression. Our findings indicate that, apart from proto-oncogene overexpression, other mechanisms, e.g. tumor suppr essor gene inactivation, are important for glial tumorigenesis. Karyot ypic analysis makes it possible to search specifically for genetic eve nts still unknown but arising from particular chromosomal changes.