Molecular analysis of the PTEN, TP53 and CDKN2A tumor suppressor genes in long-term survivors of glioblastoma multiforme

Despite multimodal therapy, glioblastoma multiforme (GBM) is associated wit h a poor prognosis with a median survival of less than 1 year. However, a s mall number of patients with GBM shows survival times of several years. Alt hough clinical features like age and performance status at diagnosis are we ll known prognostic parameters, molecular markers for prognosis of overall survival are still lacking. Therefore, we compared 2 age- and gender-matche d groups of GBM patients with different post-operative time to tumor progre ssion (TTP), defined as 'short-term' for TTP of less than 6 months (n = 21) , and 'long-term' for TTP of more than 24 months (n = 21) for genetic alter ations of the PTEN, CDKN2A and TP53 genes as well as overexpression of the EGFR, p53 and Mdm2 proteins. For the GBMs with 'short-term' TTP vs. 'long-t erm' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutati ons in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/ 21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein i n 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied. Taken t ogether, our data indicate that mutations of the PTEN and TP53 tumor suppre ssor genes, homozygous deletion of the CDKN2A gene as well as overexpressio n of the EGFR, p53 and Mdm2 proteins lack prognostic significance for overa ll survival time in patients with GBMs.