Abstract B197: Proteomic based analysis of ovarian cancer pathways.

Recent genomic-based studies have suggested ovarian cancer is a disease of copy instability, with 63 regions of focal amplification, rather than a disease driven by mutation. However, this analysis has been unable to identify changes in protein expression, modification, and activity. In this study we developed a highly quantitative MS/MS approach to examine the ratio of protein levels, combining TMT labeling with a number of motif and site-specific antibodies to identify deregulated signaling pathways between tumor and normal specimens. We identified over 1400 uniquely upregulated proteins, and over 1600 upregulated post-translational modification sites across 79 tumors and 19 normal tissue samples. We were able to survey activity of over 400 kinases and over 100 other enzymes as well as the substrates associated with them. Our study was able to map these upregulated proteins based on abundance and activity level to their regions of focal amplifications. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels. This approach may reveal new connections among pathways and candidates for therapeutics and diagnostics. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B197. Citation Format: Klarisa Rikova, Benjamin Hall, Tyler Levy, Anthony Possemato, Yi Wang, Kimberly Lee, Joan MacNeil, Ailan Guo, Daniel Mulhern, Caroline Keroack, Jian M. Ren, Sean A. Beausoleil, Scott Lonning, Michael J. Comb. Proteomic based analysis of ovarian cancer pathways. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B197.