Abstract 94: Epigenetic silencing of CDO1 sustains viability of breast cancer cells via the reduction of cellular ROS

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Approaches to analyze genome-wide methylation changes have become an extraordinary useful tool to identify thousands of new candidate hypermethylated genes in cancer. Numerous comprehensive approaches have been initiated to begin to understand the biological significance of the vast amount of methylation data generated and by this, novel tumor suppressor genes, biomarkers for early detection and prognosis prediction of cancer, and molecular mechanisms underlying tumor growth control have been discovered. In this study, we explore the candidate hypermethylated gene Cysteine Dioxygenase Type 1 (CDO1), which was recently identified in breast cancer using a functionally proven genome-wide gene expression approach. Here, we show that the epigenetic inactivation of CDO1 enhances tumor growth and sustains viability of breast cancer cells via the reduction of cellular ROS. Moreover, we observed a cancer stage-dependent increase in CDO1 methylation frequency (DCIS: 50%, stage 1-2: 65% and stage 3-4: 90%) that coincides with elevated oxidative stress levels in advanced cancers. These findings support the hypothesis that cancer cells upregulate their antioxidant capacity in adaptation to intrinsic oxidative stress. Lastly, we correlated CDO1 methylation status with clinicopathologic patient characteristics in a cohort of 186 patients. Methylation of CDO1 is significantly associated with prognostic parameters such as tumor stage, lymphovascular and perinodal invasion and predicts worse patient outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 94. doi:1538-7445.AM2012-94