Journal
EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume 101, Issue 1, Pages 150-156Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2016.07.010
Keywords
Cholangiocarcinoma; Next-generation sequence analysis; Bile
Categories
Funding
- Fund of the Biomedical Research Institute, Chonbuk National University Hospital (CNUH-BRI)
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [2014R1A2A1A10054634]
- National Research Foundation of Korea [2014R1A2A1A10054634] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Genome-wide association study in diffusely infiltrating type cholangiocarcinoma (CC) can be limited due to the difficulty of obtaining tumor tissue. We aimed to evaluate the genomic alterations of diffusely infiltrating type CC using next-generation sequencing (NGS) of bile and to compare the variations with those of mass-forming type CC. A total of 24 bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP) and 17 surgically obtained tumor tissue samples were evaluated. Buffy coat and normal tissue samples were used as controls for a somatic mutation analysis. After extraction of genomic DNA, NGS analysis was performed for 48 cancer related genes. There were 27 men and 14 women with a mean age of 65.0 +/- 11.8 years. The amount of extracted genomic DNA from 3 cm(3) of bile was 66.0 +/- 84.7 pg and revealed a high depth of sequencing coverage. All of the patients had genomic variations, with an average number of 19.4 +/- 2.8 and 22.3 +/- 3.3 alterations per patient from the bile and tumor tissue, respectively. After filtering process, damaging SNPs (8 sites for each type of CC) were predicted by analyzing tools, and their target genes showed relevant differences between the diffusely infiltrating and mass -forming type CC. Finally, in somatic mutation analysis, tumor -normal paired 14 tissue and 6 bile samples were analyzed, genomic alterations of EGFR, FURL ABL1, PIK3CA, and CDKN2A gene were seen in the diffusely infiltrating type CC, and TP53, KRAS, APC, GNA11, ERBB4, ATM, SMAD4, BRAF, and ID111 were altered in the mass -forming type CC group. STK11, GNAQ, RBI, KDR, and SMO genes were revealed in both groups. The NGS analysis was feasible with bile sample and diffusely infiltrating type CC revealed genetic differences compared with mass -forming type CC. Genome-wide association study could be performed using bile sample in the patients with CC undergoing ERCP and a different genetic approach for accurate diagnosis, pathogenesis study, and targeted therapy will be needed in diffusely infiltrating type CC. (C) 2016 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available