Abstract 2154: Molecular allelo-karyotyping of pulmonary adenocarcinoma using high resolution single nucleotide polymorphism genomic arrays

Abstract

Abstract Background Lung cancer is the leading cause of cancer death in Japan. Adenocarcinoma is the most common form of lung cancer with poor-prognosis due to late-stage detection and resistance to conventional treatment. The complexity of the genetic alterations confer pulmonary adenocarcinomas with marked patterns of gene expression. It is now critical to unravel the mechanisms which underlie a subset of tumor and they should have a significant impact in selecting patients for targeted therapy. Novel SNP-chip high resolution molecular allelo-karyotyping analysis allows us to examine global DNA copy number changes and allelic loss to evaluate allele-specific gene dosage in cancer cells. Methods A series of consecutive 111 lung adenocarcinomas, including 10 cases harboring EML4-ALK fusion, were analyzed using Affymetrix GeneChip and our robust algorithm, CNAG/AsCNAR, to perform sensitive analysis of copy number alteration and allelic composition. This robust algorithm also enabled sensitive detection of loss of heterozygosity. Clinicopathological profiles including age, gender, smoking status, WHO histology subtypes, pathological stage and clinical outcome were also examined. Genomic profiles in the selected amplified and deleted regions were obtained. Results Chromosomal arm gains of 1q, 3q, 5p, 6p, 7p, 8q, 16p and 17q were detected, while frequent loss was found in 1p, 3p, 6q, 8p, 9p, 10q and 17p. Gene alteration profiles of known oncogenes and tumor suppressor genes were obtained with this procedure. Highly amplified regions included TERT (61.3%), MYC (45.9%), EGFR (44.1%), TNFSF6B (44.1%). Homozygous deletion was noted only in 9p23.3 (5.4%, CDKN2A, CDKN2B). Cases with EML4-ALK fusion were found to be less amplified in top 15 selected regions. Lymphatic invasion positive cases revealed distinct genomic profiles compared to negative ones. Conclusion Global analysis of gene expression using high resolution SNP genomic arrays can provide a broader view of genomic alterations. Genomic amplification and loss profiles differ according to clinicopathological aspects and genomic background. 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 2154.