Ultra-Sensitive Detection of Mutant KRAS in Circulating Tumor DNA Predicts Survival in Resectable Pancreatic Adenocarcinoma
Over 90% of pancreatic adenocarcinoma (PDAC) has a KRAS mutation, 98% of which aresingle-base missense variants occurring at codon 12 (G12), codon 13 (G13), or codon 61 (Q61), with numerous studies demonstrating their clinical utility. Mutant KRAS has been detected in circulating tumor DNA (ctDNA) at all stages of PDAC using analysis methods such as next-generation sequencing (NGS). This study aimed to investigate the prognostic potential of KRAS G12, G13, and Q61 mutations present in circulating tumor DNA (ctDNA) prior to treatment initiation in localized PDAC using both standard depth (20,000x) and ultra-deep (>100,000) sequencing. Standard depth sequencing identified pathogenic KRAS mutations (G12/G13/Q61) in 11 patients. Ultra-deep sequencing demonstrated a 46% increase in detection, identifying mutant KRAS in these same 11 patients and an additional 7 patients deemed mutation-negative by standard assay.