TERC identified as a probable target within the 3q26 amplicon that is detected frequently in non-small cell lung cancers.
OBJECTIVE
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.


METHODS
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.
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
Sana
S
Yokoi
Kohichiroh
K
Yasui
Toshihiko
T
Iizasa
Issei
I
Imoto
Takehiko
T
Fujisawa
Johji
J
Inazawa
D015152:Blotting, Northern; D015139:Blotting, Southern; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D004247:DNA / Q000737:chemistry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
C422952:telomerase RNA; D012313:RNA; D004247:DNA; D019098:Telomerase