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

Authors
Hee Seung LeeEunYoung KimJINYOUNG LEEseongjoon parkho kyoung hwangCHANHEE PARK조세영Chang Moo KangSeung-Mo HongHuapyong KangJUNG HYUN JOINRAE CHOMoon Jae ChungJEONG YOUP PARKSeung Woo ParkSI YOUNG SONGJung Min HanSANGWOO KIMSeungmin Bang
Issue Date
Mar-2021
Publisher
ELSEVIER
Keywords
Pancreatic ductal adenocarcinoma; Conditionally reprogrammed cell lines; Next-generation sequencing; Patient-derived cancer cell line; Precision medicine
Citation
EBioMedicine, v.65
Journal Title
EBioMedicine
Volume
65
URI
https://yscholarhub.yonsei.ac.kr/handle/2021.sw.yonsei/5256
DOI
1016/j.ebiom.2021.103218
ISSN
2352-3964
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 © 2021 The Authors
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College of Medicine > 의과대학 외과학교실 > 1. Journal Articles
College of Medicine > 의과대학 내과학교실 > 1. Journal Articles
약학대학 > 약학대학 약학과 > 1. Journal Articles
College of Medicine > 의과대학 의학통계학과 > 1. Journal Articles

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