Purpose: Cell lines derived from non-small cell lung cancers (NSCLCs) revealed frequent high-level gains of chromosomal DNA at 3q23-q29 when examined by comparative genomic hybridization (CGH). Within this amplicon, a minimal common region of amplification in lung tumors had been mapped to 3q26 by earlier studies. The aim of the present work was to identify specific targets of the 3q26 amplification in NSCLCs.
Experimental design: We examined genomic alterations in 19 NSCLC cell lines (10 derived from squamous cell carcinomas and 9 from adenocarcinomas) by using CGH and fluorescence in situ hybridization. We determined amplification and expression levels of four candidates (EVI1, TERC, SNO, and PIK3CA) in those cell lines and also in 25 primary NSCLC tumors. Because the TERC gene encodes the RNA component of human telomerase, we examined telomerase activity by the telomeric repeat amplification protocol (TRAP) assay.
Results: Copy numbers of EVI1 and TERC increased more than those of SNO and PIK3CA in our panel of NSCLC cell lines. Significant correlation between amplification and expression levels was observed only for TERC (P = 0.006), however, among these four candidate genes. Expression of TERC was also up-regulated in 24 (96%) of 25 primary NSCLC tumors compared with their nontumorous counterparts (P = 0.0001), and elevated expression of TERC was associated with high levels of telomerase activity (P = 0.048).
Conclusions: TERC is a likely target of the 3q26 amplification, and, therefore, may be a useful biomarker for diagnosis and an attractive, novel target for molecular therapy of NSCLC.