Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments

Sung-Yup Cho, Chang Ohk Sung, Jeesoo Chae, Jieun Lee, Deukchae Na, Wonyoung Kang, Jinjoo Kang, Seoyeon Min, Ahra Lee, Eunhye Kwak, Jooyoung Kim, Boram Choi, Hyunsoo Kim, Jeffrey H. Chuang, Hyo-Kyung Pak, Chan-Sik Park, Sanghui Park, Young Hyeh Ko, Dakeun Lee, Jin Roh, Min-Sun Cho, Seongyeol Park, Young Seok Ju, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, James Keck, Jacques Banchereau, Edison T. Liu, Woo-Ho Kim, Hansoo Park, Han-Kwang Yang, Jong-Il Kim and Charles Lee

Key points

  • EBV-induced diffuse large B cell lymphomas (DLBLs) are characterized by genomic and transcriptomic alterations in the Rho pathway.

  • Targeting the Rho pathway using a ROCK inhibitor, fasudil, inhibited tumor growth in EBV-positive DLBL patient-derived xenograft models.


Epstein-Barr virus (EBV)-positive diffuse large B cell lymphomas (EBV+-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV+-DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV+-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV+-DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a ROCK inhibitor, fasudil, markedly decreased tumor growth in EBV+-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.

  • Submitted July 19, 2017.
  • Accepted February 13, 2018.