Abstract B30: Differential network reprogramming by distinct activating K-Ras mutations

In colon cancer, KRAS is most frequently mutated at codon 12, but a significant fraction of patients have mutations at codon 13. Clinical data suggest different outcomes and responsiveness to treatment between these two groups. To investigate the differential effects upon cell status associated with KRAS mutations we performed a quantitative analysis of the proteome and phospho-proteome of isogenic SW48 colon cancer cell lines. Parental cells were compared with cells in which one allele of the endogenous gene has been edited to harbour specific KRAS mutations (G12V, G12D or G13D). Each mutation generates a distinct signature, although the codon 12 mutants overlap significantly whereas G13D is highly divergent and shows more potent up-regulation of phosphopeptide responses. Codon-specific responses within our dataset will be highlighted. Our work raises fundamental questions about basic Ras biology with implications for the design and interpretation of large-scale comparative studies analysing oncogenic Ras signalling. Furthermore, the application of SILAC based quantitative proteomics within a panel of isogenic cell lines represents a promising pipeline for target and biomarker discovery. Citation Format: Dean E. Hammond, Craig J. Mageean, Emma V. Rusilowicz, Michael J. Clague, Ian A. Prior. Differential network reprogramming by distinct activating K-Ras mutations. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B30. doi: 10.1158/1557-3125.RASONC14-B30