Abstract 1380: Clinical relevance of cell-free DNA analysis for bile juice assessed through amplicon-based deep sequencing in bile duct and pancreatic cancer patients with obstructive jaundice

Abstract

Abstract Personalized treatment for patients with pancreatic or bile duct cancer is limited because cancer cells could not be detected in some patient. Cell-free DNA (cfDNA) sequencing is expected to enable a precision oncology approach for these patients. The development of gene panel for cfDNA covering hundreds of mutation hotspots is important for the establishment of clinically practical cfDNA detection system. We enrolled 40 patients with bile duct or pancreatic cancer which caused obstructive jaundice. Amplicon-based genomic profiling of 14 genes, which are commonly mutated in digestive cancer, in preoperative bile juice by next-generation sequencing (NGS) was carried out to evaluate the feasibility of this assay, and was compared with their clinical parameters. One or more somatic mutation(s) of the 14 genes in bile cfDNA were detected in 25 patients (62.5%) with bile duct or pancreatic cancer. Mutations in TP53, KRAS and APC genes were detected in 19 (47.5%), 11 (27.5%) and 4 (10.0%) patients, respectively. Mutant allele frequencies in plasma were not associated with CEA nor CA19-9. Of the 40 patients with bile duct or pancreatic cancer, the cancer cells could be detected by cytology in 18 patients (45.0%). On the other hand, mutant alleles from cancer cells could be detected in 14 patients who showed negative cytology. Hence, 32 patients (80.0%) could be diagnosed as cancer before surgical operation by using the information from liquid biopsy (cfDNA analysis using bile juice) in addition to that from cytology. Our data confirmed that mutant allele in bile cfDNA could be sensitively detected by amplicon-based NGS system. These results suggest that the detection of cfDNA in bile juice using high-sensitive deep sequencing system could be a novel diagnostic tool, and these technologies could increase the ratio of definitive diagnosis of refractory cancer such as bile duct or pancreatic cancer. Citation Format: Marie Muramatsu, Marie Muramatsu, Hiromichi Ito, Hitoshi Zembutsu. Clinical relevance of cell-free DNA analysis for bile juice assessed through amplicon-based deep sequencing in bile duct and pancreatic cancer patients with obstructive jaundice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1380.