Genome-wide screening of genomic alterations and their clinicopathologic implications in non-small cell lung cancers.
OBJECTIVE
Although many genomic alterations have been observed in lung cancer, their clinicopathologic significance has not been thoroughly investigated. This study screened the genomic aberrations across the whole genome of non-small cell lung cancer cells with high-resolution and investigated their clinicopathologic implications.


METHODS
One-megabase resolution array comparative genomic hybridization was applied to 29 squamous cell carcinomas and 21 adenocarcinomas of the lung. Tumor and normal tissues were microdissected and the extracted DNA was used directly for hybridization without genomic amplification. The recurrent genomic alterations were analyzed for their association with the clinicopathologic features of lung cancer.


RESULTS
Overall, 36 amplicons, 3 homozygous deletions, and 17 minimally altered regions common to many lung cancers were identified. Among them, genomic changes on 13q21, 1p32, Xq, and Yp were found to be significantly associated with clinical features such as age, stage, and disease recurrence. Kaplan-Meier survival analysis revealed that genomic changes on 10p, 16q, 9p, 13q, 6p21, and 19q13 were associated with poor survival. Multivariate analysis showed that alterations on 6p21, 7p, 9q, and 9p remained as independent predictors of poor outcome. In addition, significant correlations were observed for three pairs of minimally altered regions (19q13 and 6p21, 19p13 and 19q13, and 8p12 and 8q11), which indicated their possible collaborative roles.


CONCLUSIONS
These results show that our approach is robust for high-resolution mapping of genomic alterations. The novel genomic alterations identified in this study, along with their clinicopathologic implications, would be useful to elucidate the molecular mechanisms of lung cancer and to identify reliable biomarkers for clinical application.
Kim
Tae-Min
TM
Department of Microbiology, College of Medicine, Catholic University of Korea, Socho-gu, Seoul, Korea.
Yim
Seon-Hee
SH
Lee
Jung-Sook
JS
Kwon
Mi-Seon
MS
Ryu
Jae-Wook
JW
Kang
Hyun-Mi
HM
Fiegler
Heike
H
Carter
Nigel P
NP
Chung
Yeun-Jun
YJ
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D016678:Genome; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D046228:Microarray Analysis; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000235:genetics; D015996:Survival Rate
D004273:DNA, Neoplasm