Establishment and characterization of new tumor xenografts and cancer cell lines from EBV-positive nasopharyngeal carcinoma

Weitao Lin, Yim Ling Yip, Lin Jia, Wen Deng, Hong Zheng, Wei Dai, Josephine Mun Yee Ko, Kwok Wai Lo, Grace Tin Yun Chung, Kevin Y. Yip, Sau-Dan Lee, Johnny Sheung-Him Kwan, Jun Zhang, Tengfei Liu, Jimmy Yu-Wai Chan, Dora Lai-Wan Kwong, Victor Ho-Fun Lee, John Malcolm Nicholls, Pierre Busson, Xuefeng LiuAlan Kwok Shing Chiang, Kwai Fung Hui, Hin Kwok, Siu Tim Cheung, Yuk Chun Cheung, Chi Keung Chan, Bin Li, Annie Lai-Man Cheung, Pok Man Hau, Yuan Zhou, Chi Man Tsang, Jaap Middeldorp, Honglin Chen, Maria Li Lung, Sai Wah Tsao

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The lack of representative nasopharyngeal carcinoma (NPC) models has seriously hampered research on EBV carcinogenesis and preclinical studies in NPC. Here we report the successful growth of five NPC patient-derived xenografts (PDXs) from fifty-eight attempts of transplantation of NPC specimens into NOD/SCID mice. The take rates for primary and recurrent NPC are 4.9% and 17.6%, respectively. Successful establishment of a new EBV-positive NPC cell line, NPC43, is achieved directly from patient NPC tissues by including Rho-associated coiled-coil containing kinases inhibitor (Y-27632) in culture medium. Spontaneous lytic reactivation of EBV can be observed in NPC43 upon withdrawal of Y-27632. Whole-exome sequencing (WES) reveals a close similarity in mutational profiles of these NPC PDXs with their corresponding patient NPC. Whole-genome sequencing (WGS) further delineates the genomic landscape and sequences of EBV genomes in these newly established NPC models, which supports their potential use in future studies of NPC.
Original languageEnglish
Article number4663
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018

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