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.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Yoo HY,Sung MK,Lee SH,Kim S,Lee H,Park S,Kim SC,Lee B,Rho K,Lee JE,Cho KH,Kim W,Ju H,Kim J,Kim SJ,Kim WS,Lee S,Ko YHdoi
10.1038/ng.2916subject
Has Abstractpub_date
2014-04-01 00:00:00pages
371-5issue
4eissn
1061-4036issn
1546-1718pii
ng.2916journal_volume
46pub_type
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