Abstract 5171: An integrated analysis of copy number alteration and global gene expression reveals potential oncogenes underlying stomach cancer

Abstract

Abstract Although several studies had been carried out to elucidate causative copy number alteration (CNA) underlying stomach carcinogenesis, deeper understanding of CNA accumulations in stomach cancer genome in association with age and histo-pathological subtypes remains still mysterious. Here, we report an integrated analysis of genome-wide copy number alteration and global mRNA expression of 40 stomach cancer tissues from 19 old and 21 young patients using aCGH and microarray. We identified that stomach cancer genomes showed recurrent amplifications at 17q12 (ERBB2 amplicon) and 7q31.1-7q31.31 (MET amplicon), and homozygous deletions at 9p21.3 and 17p12 regions harboring tumor suppressor genes. The most frequent gained regions were 3q26.2 (45%), 7p21.1 (>50%), 7p12.2 (∼50%), 8q21.11-8q21.12 (45%), 8q22.3 (45%), 8q24.21 (45%), 8q24.22 (45%), 8q24.3 (45%), 20q12 (45%) and 20q13.2 (45%). The most frequent deleted regions were 21p11.1 (∼50%), 19p13.2 (45%), 19p13.3 (45%), 4q12 (40%), 3p21.31 (40%) and 1p35.3 (40%). Whereas young stomach cancer genomes showed more frequent gains at 7q21-7q31 than old cancer genomes, old stomach cancer genomes exhibited more recurrent gains at 8q12-8q24 and 1p12-1q42 than young cancer genomes, providing a clue about evolution of CNA accumulation in stomach cancer genome. Hierarchical expression clustering of 506 (in amplified regions) and 60 (in regions showing homozygous deletion) genes across the 40 stomach cancer samples reclassified pathological and histological subtypes based on expression pattern. Our integrated analysis of aCGH and microarray gene expression identified a pool of potential candidate stomach oncogenes and tumor suppressor genes. SiRNA-based interference of genes in MET amplicon and ERBB2 amplicon in stomach cancer cell lines significantly suppressed cell proliferation and migration, suggesting that they could be novel potential oncogenes in stomach cancer. Taken together, this study improves our understanding of stomach cancer genome evolution during CNA accumulation process and provides a new gene set of novel potential oncogenes and tumor suppressor genes that are essential for developing novel diagnostic biomarker and therapeutics for stomach cancer. Citation Format: Kyoung Song, Ryong Nam Kim, Sinyoung Jeon, Hae In Kim, Yoon-La Choi, Young Kee Shin. An integrated analysis of copy number alteration and global gene expression reveals potential oncogenes underlying stomach cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5171. doi:10.1158/1538-7445.AM2014-5171