Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma
Abstract. PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R. METHODS PDAC samples were tested using DNA and RNA sequencing. MAPK activation score and tumor microenvironment were analyzed from RNA expression data. Real-world overall survival (OS) obtained from insurance claims data was calculated from tissue collection to last contact. Significance was determined by X2 and Fisher-Exact tests. RESULTS 3,755 PDAC patients harboring KRAS G12D (n = 1,766), G12V (n = 1,294) G12R (n = 621) or G12C (n = 74) variants were identified. Patients with G12R mutations had longer OS compared to G12D overall (12.7 vs 10.1 months, p-value=0.0001), with similar trends in patients treated with gemcitabine/nab-paclitaxel (13.5 vs 10
