Oncotarget

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

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

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Oncotarget. 2017; 8:96482-96495. https://doi.org/10.18632/oncotarget.19946

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Abstract

Tsun Yee Tsang1,2, Wei Wei1,2, Hiroaki Itamochi3, Rosemary Tambouret1 and Michael J. Birrer1,2

1 Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA

2 Harvard Medical School, Boston, Massachusetts, USA

3 Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori, Japan

Correspondence to:

Michael J. Birrer, email:

Keywords: clear cell ovarian cancer, PRKCI, genomics, microarray, therapeutic target

Received: April 07, 2017 Accepted: May 29, 2017 Published: August 04, 2017

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.


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