Development of a molecular barcode detection system for pancreaticobiliary malignancies and comparison with next-generation sequencing

Abstract

BackgroundObtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA. MethodsTwo in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients. We measured the yield of DNA and compared the genomic profiles of liquid samples obtained using the non-MB panel and the MB panel. The utility of the panels in detecting druggable mutations was investigated. ResultsA significantly greater amount of DNA was obtained from bile supernatants and precipitates compared to tumor samples (P < 0.001 and P = 0.001, respectively). The number of mutations per patient was significantly higher using the MB panel than using the non-MB panel (2.8 vs. 1.3, P = 0.002). Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel (P = 0.023). Five drug-matched mutations were detected in liquid samples. ConclusionsLiquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA.