Global DNA hypomethylation-induced Delta Np73 transcriptional activation in non-small cell lung cancer

p73 possesses an extrinsic P1 promoter and an intrinsic P2 promoter controlling the expression of the pro-apoptotic TAp73 isoforms and the anti-apoptotic Delta Np73 isoforms respectively In this study we investigated the DNA methylation status of both promoters as a means of epigenetic transcriptional control of their corresponding isoforms in 102 primary non-small cell lung carcinomas (NSCLCs) We demonstrated that while P1 hypermethylation-associated reduction of TAp73 mRNA levels is relatively infrequent the P2 hypomethylation-associated over-expression of Delta Np73 mRNA is a frequent event particularly among squamous cell carcinomas P2 hypomethylation strongly correlated with LINE-1 element hypomethylation indicating that Delta Np73 over-expression may be a passive consequence of global DNA hypomethylation (c) 2010 Elsevier Ireland Ltd All rights reserved