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 Liu, Alan 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 () and Sai Wah Tsao ()
Additional contact information
Weitao Lin: The University of Hong Kong
Yim Ling Yip: The University of Hong Kong
Lin Jia: The University of Hong Kong
Wen Deng: The University of Hong Kong
Hong Zheng: The University of Hong Kong
Wei Dai: The University of Hong Kong
Josephine Mun Yee Ko: The University of Hong Kong
Kwok Wai Lo: The Chinese University of Hong Kong
Grace Tin Yun Chung: The Chinese University of Hong Kong
Kevin Y. Yip: The Chinese University of Hong Kong
Sau-Dan Lee: The Chinese University of Hong Kong
Johnny Sheung-Him Kwan: The Chinese University of Hong Kong
Jun Zhang: The University of Hong Kong
Tengfei Liu: The University of Hong Kong
Jimmy Yu-Wai Chan: The University of Hong Kong
Dora Lai-Wan Kwong: The University of Hong Kong
Victor Ho-Fun Lee: The University of Hong Kong
John Malcolm Nicholls: The University of Hong Kong
Pierre Busson: Paris-Saclay University, CNRS
Xuefeng Liu: Georgetown University Medical Center
Alan Kwok Shing Chiang: The University of Hong Kong
Kwai Fung Hui: The University of Hong Kong
Hin Kwok: The University of Hong Kong
Siu Tim Cheung: The Chinese University of Hong Kong
Yuk Chun Cheung: The University of Hong Kong
Chi Keung Chan: The University of Hong Kong
Bin Li: The University of Hong Kong
Annie Lai-Man Cheung: The University of Hong Kong
Pok Man Hau: The Chinese University of Hong Kong
Yuan Zhou: The Chinese University of Hong Kong
Chi Man Tsang: The University of Hong Kong
Jaap Middeldorp: Department of Pathology, Cancer Center Amsterdam
Honglin Chen: The University of Hong Kong
Maria Li Lung: The University of Hong Kong
Sai Wah Tsao: The University of Hong Kong

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06889-5

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