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Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
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Genomic Alterations in Biliary Tract Cancer Using Targeted Sequencing.
Kwai Han Yoo1, Nayoung K D Kim2, Woo Il Kwon3
1Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Translational Oncology
|June 9, 2016
Summary
Patient-derived tumor cell (PDC) models effectively capture genetic alterations in biliary tract cancers (BTCs). These models are crucial for identifying new therapeutic strategies and advancing targeted drug development for BTCs.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Biliary tract cancers (BTCs) encompass rare and heterogeneous tumors, including intrahepatic and extrahepatic bile duct and gallbladder adenocarcinomas.
- Patient-derived tumor cell (PDC) models offer a valuable platform for genomic analysis to address clinical challenges in BTC treatment.
Purpose of the Study:
- To establish and characterize patient-derived tumor cell (PDC) models from biliary tract cancers (BTCs).
- To perform comprehensive genome analysis on PDCs and primary tumors to identify key molecular alterations.
- To evaluate the utility of PDC models in uncovering driver mutations and informing targeted therapy strategies for BTCs.
Main Methods:
- Collected 40 BTC patient samples (January 2012 - June 2015).
- Isolated and cultured PDCs from surgical specimens, biopsies, and malignant effusions (ascites, pleural fluid).
- Conducted targeted panel sequencing and digital multiplexed gene analysis on PDCs and primary tumors.
Main Results:
- Successfully established PDC models in 27 out of 40 samples (67.5%), with higher success rates from body fluids (91.7%) compared to tissue specimens (31.3%).
- Identified 15 common mutations across diverse genetic alterations in 19 BTC cases, with TP53 mutations being the most frequent (42.1%).
- Detected various other mutations including NRAS, KRAS, ERBB2, and PIK3CA, alongside ERBB2 amplification.
Conclusions:
- PDC models are highly promising for discovering driver mutations in BTC.
- These models facilitate the identification of rational therapeutic strategies for BTC.
- The application of PDC models is expected to guide clinical trials for molecular-based targeted therapies in BTC.
