| Literature DB >> 24584070 |
Hae Yong Yoo1, Min Kyung Sung2, Seung Ho Lee3, Sangok Kim4, Haeseung Lee4, Seongjin Park5, Sang Cheol Kim5, Byungwook Lee5, Kyoohyoung Rho6, Jong-Eun Lee6, Kwang-Hwi Cho7, Wankyu Kim4, Hyunjung Ju8, Jaesang Kim4, Seok Jin Kim9, Won Seog Kim9, Sanghyuk Lee4, Young Hyeh Ko10.
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.Entities:
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Year: 2014 PMID： 24584070 DOI： 10.1038/ng.2916
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330