Abstract 2539 Defining the Molecular Heterogeneity and Functional Impact of Pancreatic Cancer-Associated KRAS Mutations

KRAS mutations are the initiating factor in approximately 93% of pancreatic adenocarcinoma (PDAC). Consequently, we investigated the molecular landscapes shaped by the six most common PDAC-associated KRAS mutations (G12D, G12R, G12V, Q61H, Q61K, Q61R) to better understand PDAC-initiating signaling. We engineered human pancreatic ductal epithelial cells (HPNE) for inducible expression of KRAS mutants and conducted multi-tiered analyses. These included transcriptomic profiling using Bulk RNA-seq, proteomic cytokine analysis with the Human Cytokine 96-Plex Discovery Assay, and phosphoproteomic profiling through the Phospho Explorer Array.