Abstract 2155: Genetics of Primary and Metastatic Ovarian Cancer
Authors: Shannon MacLaughlan, Andrew Fischer, Katrin Kristjansdottir, Anna Ritz, Ben Raphael, Margaret Steinhoff, Alexander Brodsky, Laurent Brard
Journal: Cancer Research (2010)

Abstract Objective: The purpose of this study is to determine the differential copy number abnormalities (CNA) in primary serous epithelial ovarian cancer (EOC) and matched EOC metastatic specimens utilizing comparative genomic hybridization (CGH) technology. We are testing the hypothesis that comparing amplified and deleted regions that are similar or different between primary and metastatic may identify key drivers of metastasis and highlight genetic changes that occur during metastasis. Amplified regions lost in the metastatic tumor may indicate loci not required for progression and more aggressive disease. Finally, expression of genes in amplified and deleted regions will be measured to determine if their expression is indeed driven by the copy number. Materials: Primary and metastatic serous EOC tumors were collected from patients at the time of their initial cytoreductive surgery. Eligible patients were postmenopausal and presented with a pelvic mass, an elevated tumor marker (CA125 or HE4), signs of metastatic EOC on exam or imaging, and had never received chemotherapy. All women provided signed informed consent as part of an IRB-approved protocol. Primary and metastatic EOC specimens were confirmed by a dedicated gynecologic pathologist to be serous histology and were analyzed with the Agilent 4×180K aCGH platform, using DNA from each patient's blood as a matched control. The magnitude of deletions and amplifications in CNAs measured over the whole genome were determined by a combination of Nexus and in-house software. Results: Among the eight patients eligible for analysis, the median age was 68 years (range 54-78); six (75%) were Caucasian; one was Hispanic (12.5%) and one (12.5%) was African-American. All patients had high grade serous EOC. The majority of patients (87.5%) had stage IIIc disease, and one woman had stage IIc disease. Primary and metastatic serous EOC tumor DNA demonstrated frequent amplifications and deletions when compared to matched controls. Preliminary analyses of EOC tumors demonstrated amplifications and deletions unique to metastatic specimens as compared to their matched primary EOC tumors. Regions affected included amplifications and deletions known to be associated with therapeutic responses. Comparison to publically available larger primary tumor copy number data is revealing recurrent specific regions that are preserved in the metastatic tumors while others are not suggesting importance for tumor progression. Conclusions: Genomic analysis of EOC may elucidate pathways of carcinogenesis and metastasis. Genes that are amplified in primary tumors but disappear in corresponding metastases may represent regions that are not critical for tumor growth and progression. Genes that are amplified in metastatic implants may represent important loci for metastatic potential of EOC, and could ultimately represent potential targets for therapies. 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 2155.