STUDY ON ANEUPLOIDY AND P53 MUTATIONS IN ASTROCYTOMAS

To determine whether a correlation exists between aneuploidy and p53 s tatus in astrocytic tumors we analyzed 48 astrocytomas with different grades of malignancy for the presence of p53 mutations and aneuploidy of chromosomes 10 and 17 (Ch10, Ch17), known to be particularly involv ed with this type of tumor We used polymerase chain reaction (PCR)-bas ed denaturing gradient gel electrophoresis (DGGE) analysis on exons 5- 8 of the p53 gene, and fluorescence in situ hybridization (FISH) analy sis on interphase nuclei using chromosome specific pericentromeric pro bes, respectively. Our results showed that Ch10/Ch17 aneuploidy is a c ommon early event in astrocytomas (90% of low grade tumors are aneuplo id). p53 mutations and Ch17 aneuploidy are early events, but their inc idence is not dependent on tumor grade. Loss of Ch10 is the only alter ation that significantly correlates with tumor progression. No signifi cant correlation between the presence of Ch10/Ch17 aneuploidy and p53 mutations was found. However, the coexistence of p53 mutations and ane uploidy, was observed in a subset of cases. The presence of p53 mutati ons appeared to be a significant predictor of a poor prognosis. In con clusion, genomic instability may or may nor be associated with p53 mut ations in astrocytomas, thus suggesting that other cellular determinan ts can also be responsible for the aneuploidy observed.