Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma,...

p53, p16 and PTEN are the most commonly altered tumor suppressor genes in human cancers. In the present study, we compared the presence of individual and multiple alterations of these tumor suppressors in non-small cell lung carcinoma (NSCLC), glioma and breast carcinoma, in order to evaluate specificity of each tumor type regarding the number of altered genes, as well as their combinations. We tested the mutational status, loss of heterozygosity and methylation status of these genes. Effects of gene alterations on patients' survival were also assessed. In NSCLC samples, single gene alterations occurred rarely, while there was considerable increase in incidence of double gene alterations. Furthermore, coexistence of aberrant p53, PTEN and p16 was the most frequent and had significant adverse effect on the survival of NSCLC patients. On the contrary, in glioma and breast cancer specimens, substantial number of cases had aberrant single gene only. Moreover, glioma and breast carcinoma also differ in genotypes that were predominant. Specifically, in glioma samples, prevalent were co-alterations of PTEN and p16, followed by aberrant only PTEN. In breast cancer samples, alterations in all three genes as well as in p53 and p16 were the most common. Moreover, PTEN was altered exclusively with aberrant p53, with statistically significant correlation among them. Overall, our results suggest that NSCLC, glioma and breast cancer need different approaches in molecular diagnosis and treatment with particular attention toward the number and combination of targeted genes.