Title

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

Document Type

Article

Publication Date

4-26-2018

JAX Source

Blood 2018 Apr 26; 131(17):1931-1941

Volume

131

Issue

17

First Page

1931

Last Page

1941

ISSN

1528-0020

PMID

29475961

DOI

https://doi.org/10.1182/blood-2017-07-797209

Grant

CA034196

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. Blood 2018 Apr 26; 131(17):1931-1941.

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