Abstract 2211: Array-comparative genomic hybridization identifies important recurrent copy number alterations in non-small cell lung cancer

Abstract

Abstract Comprehensive knowledge of the genomic aberrations involved in NSCLC may deliver improved therapies, diagnostic and prognostic biomarkers. Recurrent copy number alterations (CNA) found in the same locus across a set of tumour samples are assumed to be the site of “driver” cancer genes. We hypothesize that whole genome array comparative genomic hybridization (aCGH) will identify recurrent regions of gains and loss in NSCLC containing candidate “driver” genes. Methods: DNA from fresh-frozen tumor tissue of 133 NSCLCs were obtained from The Prince Charles Hospital lung tumour bank. aCGH was performed using Agilent CGH 44B microarrays (Agilent Technologies). Recurrent CNAs were identified using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm, controlling for false discovery rates (q≤0.005). Focal (<50% of chromosome arm) regions of amplification and deletion were identified by applying GISTIC with thresholds of log2 0.848 and −0.747, respectively, corresponding to 3.6 copies and 1.2 copies with stromal contamination of 30%. Results: Regions of amplification occurred in 3q26.33, 5p15.33, 8p11.23, 11q13.3 and 19q13.2 and deletions occurred in 3p11.2, 4p15.1, 4q34.3, 5q14.1, 6q22.31, 8p23.1, 9p21.3, 10q23.31, 11q25, 13q14.3, 15q14, 16q23.3, 17p12, 18q22.3, 21q21.3 and 22q13.33. The most significant CNA regions were deletion in 9p21.3 (q=1.20E-40) and amplification in 3q26.33 (q=1.13E-10). These regions contain known tumor suppressor genes (TSGs) (CDKN2A in 9p21.3) and oncogenes (SOX2 in 3q23.33). Conclusion: We have identified regions with recurrent CNAs in NSCLC many of which harbor known oncogenes and TSGs. Further validation will be performed using public datasets and independent test cohorts. Supported by: NHMRC Medical Postgraduate Scholarship 569762. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2211.