Comparative genomic hybridization array analysis and real time PCR reveals genomic alterations in squamous cell carcinomas of the lung

Received 1 June 2006; received in revised form 7 September 2006; accepted 20 September 2006.

Summary

Genomic alterations have been identified in lung cancer tissues and reported in numerous studies. To analyze genomic aberrations in lung cancer patients, we used array comparative genomic hybridization (array CGH) in 14 squamous cell lung carcinoma (SqC) tissues. Copy number gain and loss in chromosomal regions were detected, and the corresponding genes were confirmed by real time PCR. Several frequently altered loci, including gain of 3q (36% of samples), were found. The most frequently identified losses were found at 14q32.33 (21% of samples). The relative degree of chromosomal change was analyzed using log2 ratios. High-level DNA amplifications (>0.8 log2 ratio) were detected at 20 regions in 1p, 2q, 3q, 4q, 6q, 7p, 8q, 9p, 10q, 12q, 14q and 19p. We found that the fold change levels were highest at EVI1 (3q26.2), LPP (3q27-28) and FHF-1 (3q28) gene loci. Our results show that array CGH is a useful tool for identification of gene alteration in lung cancer, and that the above-mentioned genes might represent potential candidate genes for pathogenesis and diagnosis of lung cancer.

Keywords: Lung cancer, Squamous cell carcinoma, Array CGH, Real time PCR, Chromosomal aberration, Gene amplification

a Department of Anesthesiology, St. Mary's Hospital, The Catholic University, Seoul, South Korea

b Catholic Neuroscience Center, The Catholic University, Seoul, South Korea

c Department of Pharmacology College of Medicine, Kyung Hee University, Seoul, South Korea

d Department of Internal Medicine, Dongguk University International Hospital, Dongguk University College of Medicine, Goyang, South Korea

e Division of Pulmonary and Critical Care, Department of Medicine, College of Medicine, Catholic University, Seoul, South Korea

f Department of Internal Medicine, Korea University Medical Center, Anam Hospital, Seoul, South Korea

g Department of Thoracic Surgery, The Catholic University, Seoul, South Korea

h Department of Occupational and Environmental Medicine, St. Mary's Hospital, The Catholic University, Seoul, South Korea

Corresponding author. Tel.: +82 2 3779 1401; fax: +82 2 3481 7602.

PII: S0169-5002(06)00515-0

doi:10.1016/j.lungcan.2006.09.018

7 of 21