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

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

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