Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes

Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previously reported that the contents of endometriotic cysts, especially high concentrations of free iron, are a possible cause of OCCC carcinogenesis through iron-induced persistent oxidative stress. In this study, we conducted gene expression microarray analysis using 38 ovarian cancer cell lines and identified genes commonly expressed in both OCCC cell lines and clinical samples, which comprise an OCCC gene signature. The OCCC signature reproducibly predicts OCCC specimens in other microarray data sets, suggesting that this gene profile reflects the inherent biological characteristics of OCCC. The OCCC signature contains known markers of OCCC, such as hepatocyte nuclear factor-1β (HNF-1β) and versican (VCAN), and other genes that reflect oxidative stress. Expression of OCCC signature genes was induced by treatment of immortalized ovarian surface epithelial cells with the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1β and VCAN in OCCC cell lines. This genome-wide study indicates that the tumor microenvironment induces specific gene expression profiles that contribute to the development of distinct cancer subtypes. This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 50 print issues and online access 251,40 € per year only 5,03 € per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Similar content being viewed by others

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Author information Authors and Affiliations Corresponding author Additional information Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc) Rights and permissions About this article Cite this article Yamaguchi, K., Mandai, M., Oura, T. et al. Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes. Oncogene 29, 1741–1752 (2010). https://doi.org/10.1038/onc.2009.470 Received: Revised: Accepted: Published: Issue date: DOI: https://doi.org/10.1038/onc.2009.470

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