@article{6628b6f059da4bf7bfaed37a9e01a8ab,
title = "Alterations in the Rho pathway contribute to Epstein-Barr virus–induced lymphomagenesis in immunosuppressed environments",
abstract = "Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (EBV1-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV1-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 EBV1-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV1-DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a Rho-associated protein kinase (ROCK) inhibitor, fasudil, markedly decreased tumor growth in EBV1-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.",
author = "Cho, {Sung Yup} and Sung, {Chang Ohk} and Jeesoo Chae and Jieun Lee and Deukchae Na and Wonyoung Kang and Jinjoo Kang and Seoyeon Min and Ahra Lee and Eunhye Kwak and Jooyoung Kim and Boram Choi and Hyunsoo Kim and Chuang, {Jeffrey H.} and Pak, {Hyo Kyung} and Park, {Chan Sik} and Sanghui Park and Ko, {Young Hyeh} and Dakeun Lee and Jin Roh and Cho, {Min Sun} and Seongyeol Park and Ju, {Young Seok} and Suh, {Yun Suhk} and Kong, {Seong Ho} and Lee, {Hyuk Joon} and James Keck and Jacques Banchereau and Liu, {Edison T.} and Kim, {Woo Ho} and Hansoo Park and Yang, {Han Kwang} and Kim, {Jong Il} and Charles Lee",
note = "Funding Information: The authors thank Stephen Sampson for editing the manuscript and Asis Das for critical reading of the manuscript. This work was supported by the Korean Healthcare Technology R&D project through the Korean Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant HI13C2148 and HI16C2387); the International Research & Development Program of the National Research Foundation of Korea, funded by the Ministry of Science, ICT and Future Planning (grant no. 2015K1A4A3047851); the National Research Foundation of Korea grant, funded by the Korea government (grant 2017R1C1B2002183); and the National Cancer Institute of the National Institutes of Health (grant P30CA034196). C.L. is a distinguished Ewha Womans University Professor supported in part by the Ewha Womans University Research grant of 2015-2017. Publisher Copyright: {\textcopyright} 2018 by The American Society of Hematology.",
year = "2018",
month = apr,
day = "26",
doi = "10.1182/blood-2017-07-797209",
language = "English",
volume = "131",
pages = "1931--1941",
journal = "Blood",
issn = "0006-4971",
publisher = "Elsevier BV",
number = "17",
}