Abstract 2000: Different oncogenic KRAS mutations produce distinct heterogenous outcomes in signaling pathways of isogenic mouse embryonic fibroblasts

Background: Growing evidence points towards the concept that not all RAS allelic variances are equal. Different RAS mutations produce distinct variations in signal transduction to sustain their proliferative needs accordingly. This is an especially important concept to consider as medicine shifts towards a more personalized approach. In accordance with this notion, through this study, we aim to explore the network dynamics and pinpoint disparities in signaling events associated with seven common KRAS allelic variances in non-small cell lung carcinoma. Methods: We used Mouse Embryonic Fibroblasts (MEF) provided by the RAS initiative (https://www.cancer.gov/research/key-initiatives/ras/outreach/reference-reagents/cell-lines). MEF were engineered to selectively harbor and express either wild type KRAS (4A and 4B WT) or one of seven following mutations: 4B G12D, G12C, G12R, G12V, G13D, Q61R and Q61L. Using high throughput immunoassay, Reverse Phase Protein Microarray (RPPA), we explored broad changes in signaling dynamics across our models. Specifically, we captured expression and/or activation levels of 68 proteins and phosphoproteins including: Receptor Tyrosine Kinases, MAPK, AKT/mTOR, JNK/STAT. Data were analyzed using unsupervised hierarchical clustering analysis using the Ward methods and the Kruskal Wallis test. P values