Abstract LB-348: Identifying novel oncogenes in ovarian cancer using integrative genomics and gene-knock downs

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.LB-348-LB-348
• Main Authors: Ramakrishna, Manasa, Williams, Louise H., Bearfoot, Jennifer L., Boyle, Samantha E., Sridhar, Anita, Davis, Sally, Gorringe, Kylie L., Campbell, Ian G.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-LB-348

Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. To expedite identification of ovarian oncogenes we have integrated matching gene copy number and gene expression data from a cohort of 68 primary epithelial ovarian cancers to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (>40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 41% of these differentially expressed probesets also showed a strong positive correlation (r≥0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 43 known protein coding genes showed a strong positive correlation between expression and copy number. We have verified previously known ovarian oncogenes such as ERBB2 and also identified novel potential oncogenic drivers such as PUF60 (SIAHBP1) and TPX2. Functional characterisation and mutation analysis of these novel oncogene candidates will be presented. 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 LB-348.