Abstract B2: Alterations of p53, PTEN, and EGFR genes in glioblastoma multiforme

Glioblastomas are the most frequent and the most aggressive human brain tumors. Glioblastoma multiforme is one of the most intensively investigated human malignancy but the molecular mechanisms associated with the evolution of this type of tumor are still poorly understood. The aim of this study was to investigate alterations in EGFR oncogene and PTEN and p53 tumor supressor genes in 35 glioma specimen and to evaluate their role in glioma pathogenesis. DNA from tumor and blood of 35 patients with glioma was isolated and used to perform analysis of p53 mutational status using single-strand conformational polymorphism analysis (PCR- SSCP) and sequencing, evaluate loss of heterozigosity (LOH) in p53 and PTEN by fragment analysis, and to asseess EGFR gene amplification by differential PCR. Obtained results were further correlated with clinicopathological parameters. Loss of heterozygosity of PTEN was the most frequent alteration present in 62.86% of samples, followed by EGFR amplification detected in 40% of cases, while p53 gene was mutated in 28.57% of cases and inactivated by LOH in 20% of cases. All three genes were altered in 11.43% of samples, while 45.71 % of samples had only one of these three genes aberrant. We also identified 5 novel mutations in p53 that were not associated with brain tumors before. Correlation analysis indicated that p53 alterations were significantly associated with younger age (