Genep73: Deletions and expression in non-small-cell lung carcinoma cells

Abstract

We studied the relation between genetic anomalies in thep73 gene encoding a product structurally and functionally similar to the protein p53 and the pathogenesis of non-small-cell lung carcinoma (NSCLC; 83 patients). Loss of one of thep73 alleles was revealed in 44% (15/34) informative cases. Presence of deletions correlated with the features common for tumor development: metastatic affection of regional lymph nodes (p=0.045), large tumor size (p=0.037), advanced stage of the disease (p=0.017). Allele expression of the genep73 was studied basing on analysis of the polymorphic C/T site in the second exon. All ten studied samples of normal bronchogenic epithelium showed monoallelic expression ofp73, contrary to the six NSCLC samples which preserved both of thep73 alleles and showed biallelic expression. Enhanced expression of p73 mRNA in tumor tissue compared with normal bronchogenic epithelium was found in 28 of 34 (82.4%) NSCLC patients. Expression of p73 in NSCLC cells showed correlation neither with deletions of one of the alleles, nor with any parameter reflecting clinical pathology. The results suggest thatp73 is not a classical tumor suppressor gene in NSCLC. However, alterations ofp73 expression are common for NSCLC. This may be important for our understanding of the NSCLC origin and development.