MOLECULAR ANALYSIS OF GENOMIC ABNORMALITIES IN HUMAN GLIOMAS

A series of 57 malignant gliomas, including 27 astrocytomas grade III- IV (glioblastoma multiforme), 15 astrocytomas grade I-II, and 15 tumor s with major oligodendroglial component, was examined to detect molecu lar abnormalities of loci at specific chromosome regions. At the cytog enetic level, these regions have been shown to be nonrandomly involved in neoplastic development of these histologic subtypes of tumor. We u sed a panel of 24 polymorphic DNA probes to analyze loss of heterozygo sity (LOH) at loci on chromosomes 7, 9, 10, 13, 17p, and 22q. In addit ion, the retinoblastoma (RB1) oncosuppressor gene, the platelet-derive d growth factor A (PDGFA) gene, and the epidermal growth factor recept or (EGFR) gene were analyzed directly. Loss of genetic information on the short arm of chromosome 17 was observed in both low- and high-grad e astrocytomas, whereas no oligodendroglial tumor was characterized by this type of aberration. LOH for chromosome 10, mainly compatible wit h loss of the entire chromosome, was primarily evidenced in the more m alignant forms and in isolated cases diagnosed as low-grade astrocytom as. Again, no oligodendroglial tumor displayed losses of chromosome 10 . In contrast, four tumors with major oligodendroglial component showe d losses involving 9p markers, primarily interferon A and B (IFNA, IFN B); this feature was also observed in two low-grade astrocytomas and i n 11 high-grade tumors. Isolated cases displayed LOH for markers on ch romosomes 13 and 22, whereas EGFR amplification was almost exclusively evidenced in the more malignant forms which, in most instances, also presented LOH for chromosome 10. In general, the samples with lower ma lignancy stage displayed a lesser grade of abnormalities, mainly restr icted to losses at 17p and chromosome 10 in astrocytomas grade I-II an d at 9p in oligodendrogliomas. In contrast, about 50% of the high-grad e tumor samples analyzed included abnormalities at two or more loci, w ith a recurrent association of EGFR amplification and LOH for chromoso me 10; this association was evident in 26% of the high-grade astrocyto mas.