Integrated genomic analysis of clear cell ovarian cancers identified PRKCI as a potential therapeutic target.

Tsun Yee Tsang,Rosemary Tambouret,Hiroaki Itamochi,Michael J Birrer,Wei Wei

doi:10.18632/oncotarget.19946

Tsun Yee Tsang, Rosemary Tambouret + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.19946

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Journal: Oncotarget	Publication Date: Aug 4, 2017
Citations: 13	License type: cc-by

Affiliation: Massachusetts General Hospital, Tottori University

Abstract

Clear cell ovarian cancer (CCOC) is an epithelial ovarian cancer histotype with unique pathologic, biologic and clinical features. Despite its worse prognosis than serous ovarian cancer (SOC), the genomic landscape of CCOC is less well defined. Integrated genomic analysis of CCOC allows the identification of potential therapeutic targets to improve the treatment of this tumor. Using comparative genomic hybridization and gene expression profiling, we have screened 12 CCOC cell lines and 40 tumors to identify 45 amplified and overexpressed genes. Pathways analysis of these genes identified 19 genes with cancer-related functions. Of these, PRKCI is one of the most frequently amplified and overexpressed genes and its expression induced cancer cell proliferation and migration/invasion in vitro as well as tumor growth in vivo. Targeting PRKCI by small molecule inhibitor, sodium aurothiomalate (ATM), significantly reduced the in vivo tumor growth and may be a new therapeutic strategy to improve the treatment of CCOC.

Highlights

Ovarian cancer is the most lethal of gynecologic cancers in the United States resulting in 14,000 deaths each year [1, 2]
The genomic DNA copy status of Clear cell ovarian cancer (CCOC) was investigated by high-resolution array comparative genomic hybridization (aCGH) using Agilent human 105K oligonucleotide microarrays on 12 CCOC cell lines
Clear cell ovarian cancer is an aggressive subtype of ovarian cancer that is less responsive to chemotherapy and has a poorer prognosis

Summary

Introduction

Ovarian cancer is the most lethal of gynecologic cancers in the United States resulting in 14,000 deaths each year [1, 2]. Clear cell ovarian cancer (CCOC) is the third most common subtype of ovarian cancer, with an estimated incidence of 5 % of all epithelial ovarian malignancies [4, 5]. CCOC has a poorer prognosis than other histotypes in that patients with CCOC have higher risk of recurrence and lower survival rate when compared with patients with serous ovarian cancer. This may be partially due to the fact that these tumors are less responsive to platinum/taxanebased chemotherapy [6, 7]. The development of a more effective therapeutic approach specific for CCOC is an unmet clinical need and this will likely require the identification of new therapeutic targets

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