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Profiling of conditionally reprogrammed cell lines for in vitro chemotherapy response prediction of pancreatic cancer

Authors
 Hee Seung Lee  ;  Eunyoung Kim  ;  Jinyoung Lee  ;  Seung Joon Park  ;  Ho Kyoung Hwang  ;  Chan Hee Park  ;  Se-Young Jo  ;  Chang Moo Kang  ;  Seung-Mo Hong  ;  Huapyong Kang  ;  Jung Hyun Jo  ;  In Rae Cho  ;  Moon Jae Chung  ;  Jeong Youp Park  ;  Seung Woo Park  ;  Si Young Song  ;  Jung Min Han  ;  Sangwoo Kim  ;  Seungmin Bang 
Citation
 EBIOMEDICINE, Vol.65(103218), 2021-03 
Journal Title
 EBIOMEDICINE 
Issue Date
2021-03
Keywords
Conditionally reprogrammed cell lines ; Next-generation sequencing ; Pancreatic ductal adenocarcinoma ; Patient-derived cancer cell line ; Precision medicine
Abstract
Background: The establishment of patient-derived models for pancreatic ductal adenocarcinoma (PDAC) using conventional methods has been fraught with low success rate, mainly because of the small number of tumour cells and dense fibrotic stroma. Here, we sought to establish patient-derived model of PDAC and perform genetic analysis with responses to anticancer drug by using the conditionally reprogrammed cell (CRC) methodology. Methods: We performed in vitro and in vivo tumourigenicity assays and analysed histological characteristics by immunostaining. We investigated genetic profiles including mutation patterns and copy number variations using targeted deep sequencing and copy-number analyses. We assessed the responses of cultured CRCs to the available clinical anticancer drugs based on patient responsiveness. Findings: We established a total of 28 CRCs from patients. Of the 28 samples, 27 showed KRAS mutations in codon 12/13 or codon 61. We found that somatic mutations were shared in the primary-CRC pairs and shared mutations included key oncogenic mutations such as KRAS (9 pairs), TP53 (8 pairs), and SMAD4 (3 pairs). Overall, CRCs preserved the genetic characteristics of primary tumours with high concordance, with additional confirmation of low-AF NPM1 mutation in CRC (35 shared mutations out of 36 total, concordance rate=97.2%). CRCs of the responder group were more sensitive to anticancer agents than those of the non-responder group (P < 0.001). Interpretation: These results show that a pancreatic cancer cell line model can be efficiently established using the CRC methodology, to better support a personalized therapeutic approach for pancreatic cancer patients. Funding: 2014R1A1A1006272, HI19C0642-060019, 2019R1A2C2008050, 2020R1A2C209958611, and 2020M3E5E204028211.
DOI
10.1016/j.ebiom.2021.103218
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chang Moo(강창무) ORCID logo https://orcid.org/0000-0002-5382-4658
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Park, Seung Woo(박승우) ORCID logo https://orcid.org/0000-0001-8230-964X
Park, Jeong Youp(박정엽) ORCID logo https://orcid.org/0000-0003-0110-8606
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lee, Jin Young(이진영)
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
Chung, Moon Jae(정문재) ORCID logo https://orcid.org/0000-0002-5920-8549
Cho, In Rae(조인래)
Hwang, Ho Kyoung(황호경) ORCID logo https://orcid.org/0000-0003-4064-7776
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182237
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