A Recurrent Inactivating Mutation in RHOA GTPase in Angioimmunoblastic T Cell Lymphoma

Overview

Journal Nat Genet

Specialty Genetics

Date 2014 Mar 4

PMID 24584070

Citations 196

Authors

Hae Yong Yoo

Min Kyung Sung

Seung Ho Lee

Sangok Kim

Haeseung Lee

Seongjin Park

Sang Cheol Kim

Byungwook Lee

Kyoohyoung Rho

Jong-Eun Lee

Kwang-Hwi Cho

Wankyu Kim

Hyunjung Ju

Jaesang Kim

Seok Jin Kim

Won Seog Kim

Sanghyuk Lee

Young Hyeh Ko

Affiliations

Soon will be listed here.

Abstract

The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further examination of the RHOA mutation encoding p.Gly17Val in 239 lymphoma samples showed that the mutation was specific to T cell lymphoma and was absent from B cell lymphoma. We demonstrate that the RHOA mutation encoding p.Gly17Val, which was found in 53.3% (24 of 45) of the AITL cases examined, is oncogenic in nature using multiple molecular assays. Molecular modeling and docking simulations provided a structural basis for the loss of GTPase activity in the RHOA Gly17Val mutant. Our experimental data and modeling results suggest that the RHOA mutation encoding p.Gly17Val is a driver mutation in AITL. On the basis of these data and through integrated pathway analysis, we build a comprehensive signaling network for AITL oncogenesis.

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