Abstract 2180: Identification of genomic alterations of human serous ovarian carcinoma with genome-wide integration of copy number and gene expression analysis
Authors: Huang Ruby Y.J , Davidson Ben , Kuznetsov Vladimir , Hsieh Chang-Yao , Thiery Jean Paul 
Published: February 2011

Objective: Ovarian carcinoma is a heterogeneous entity which is characterized by high degrees of genetic instability with frequent genetic damages. This complexity has made the identification of specific genes and pathways that are pivotal for carcinoma initiation or progression difficult. Our hypothesis is that progression of ovarian carcinoma follows sequential events of epigenetic and/or genomic alterations, which will lead to continuous selections of new clones with increased aggressiveness. In the present study, we aim to explore the global genomic alterations in ovarian carcinoma and to identify the driver events.

Materials & Methods: Clinical samples were obtained from patients diagnosed with ovarian serous adenocarcinoma at The Radium Hospital (Oslo, Norway) and National Taiwan University Hospital (Taipei, Taiwan). The Oslo collection consisted of 53 malignant effusions. Effusions were submitted for routine diagnostic purposes to the Division of Pathology at the Norwegian Radium Hospital during the period 1998-2005. The tumor cell population consisted of &gt;50% in all specimens analyzed in this study. The Taipei collection consisted of 41 carcinoma tissues obtained from primary tumors at cytoreductive surgeries. Fresh-frozen tumor samples with ≥80% carcinoma parts were included in this study. DNA was extracted by using phenol chloroform/isoamyl alcohol precipitation. RNA was extracted by using Trizol. All samples were subjected for copy number (CN) analysis by using Affymetrix Genome-Wide SNP Array 6.0. 25 effusion samples were subjected for gene expression analysis by using Affymetrix U133 Plus 2 Arrays. Partek Genomics Suites was utilized for data analysis and integration.

Results: CN analysis revealed extensive CN alterations throughout the genome in these ovarian carcinoma samples. Frequency scoring on chromosome arms identified 8q and 3q as the most frequent amplified regions in both collections. The effusion collection had a higher frequency of 20q amplifications than the primary collection. Amplified regions at the entire 8q (except toward the telomere end) and 20q11-12 were found to be “stable” with continuous positive correlated regions between CN and gene expression. Regions at 3q were found to be “unstable” with interspersed regions of positive and negative correlations.

Conclusion: We conclude that amplification at 8q and 3q are frequently seen in serous ovarian carcinoma and might be essential for ovarian carcinogenesis. Most of the genes at 8q had positive CN-expression correlations which could be explained by actual gains of DNA copies. A fraction of genes at 3q displayed negative CN-expression correlations. Alterations of transcriptional regulators elsewhere could serve as the mechanism. In addition, preferential amplifications of 20q for carcinoma in effusions indicate a role in driving tumor progression.

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 2180.