| Literature DB >> 29475961 |
Sung-Yup Cho1, Chang Ohk Sung2,3, Jeesoo Chae4, Jieun Lee5, Deukchae Na1, Wonyoung Kang2,5, Jinjoo Kang5, Seoyeon Min5, Ahra Lee5, Eunhye Kwak5, Jooyoung Kim5, Boram Choi5, Hyunsoo Kim2, Jeffrey H Chuang2, Hyo-Kyung Pak3,6, Chan-Sik Park3, Sanghui Park7, Young Hyeh Ko8, Dakeun Lee9, Jin Roh3, Min-Sun Cho7, Seongyeol Park10, Young Seok Ju10, Yun-Suhk Suh11, Seong-Ho Kong11, Hyuk-Joon Lee11,12, James Keck13, Jacques Banchereau2, Edison T Liu2, Woo-Ho Kim12,14, Hansoo Park15, Han-Kwang Yang11,12, Jong-Il Kim4,12,16, Charles Lee2,5.
Abstract
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 Rho-associated protein kinase (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.Entities:
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Year: 2018 PMID： 29475961 PMCID： PMC5921963 DOI： 10.1182/blood-2017-07-797209
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113