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, The Jackson Laboratory
Jinjoo Kang
Seoyeon Min
Ahra Lee
Eunhye Kwak
Jooyoung Kim
Boram Choi
Hyunsoo Kim, The Jackson Laboratory
Jeffrey H Chuang, The Jackson Laboratory
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, The Jackson Laboratory
Edison T Liu, The Jackson Laboratory
Woo-Ho Kim
Hansoo Park
Han-Kwang Yang
Jong-Il Kim
Charles Lee, The Jackson Laboratory


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. Blood 2018 Feb 23 [Epub ahead of print]