A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma = T세포 림프종에서 빈번한 RHOA 유전자의 비활성화 돌연변이

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Title
A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma = T세포 림프종에서 빈번한 RHOA 유전자의 비활성화 돌연변이
Author(s)
H Y Yoo; Min Kyung Sung; S H Lee; S Kim; H Lee; Seongjin Park; Sang Cheol Kim; Byunguk Lee; K Rho; J E Lee; K H Cho; W Kim; H Ju; J Kim; S J Kim; W S Kim; S Lee; Y H Ko
Bibliographic Citation
Nature Genetics, vol. 46, no. 4, pp. 371-375
Publication Year
2014
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.
ISSN
1061-4036
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/ng.2916
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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