| Literature DB >> 24413737 |
Mamiko Sakata-Yanagimoto1, Terukazu Enami1, Kenichi Yoshida2, Yuichi Shiraishi3, Ryohei Ishii4, Yasuyuki Miyake5, Hideharu Muto5, Naoko Tsuyama6, Aiko Sato-Otsubo7, Yusuke Okuno8, Seiji Sakata9, Yuhei Kamada5, Rie Nakamoto-Matsubara5, Nguyen Bich Tran5, Koji Izutsu10, Yusuke Sato7, Yasunori Ohta11, Junichi Furuta12, Seiichi Shimizu13, Takuya Komeno14, Yuji Sato15, Takayoshi Ito16, Masayuki Noguchi17, Emiko Noguchi18, Masashi Sanada7, Kenichi Chiba3, Hiroko Tanaka19, Kazumi Suzukawa20, Toru Nanmoku21, Yuichi Hasegawa5, Osamu Nureki4, Satoru Miyano22, Naoya Nakamura23, Kengo Takeuchi24, Seishi Ogawa2, Shigeru Chiba25.
Abstract
Angioimmunoblastic T cell lymphoma (AITL) is a distinct subtype of peripheral T cell lymphoma characterized by generalized lymphadenopathy and frequent autoimmune-like manifestations. Although frequent mutations in TET2, IDH2 and DNMT3A, which are common to various hematologic malignancies, have been identified in AITL, the molecular pathogenesis specific to this lymphoma subtype is unknown. Here we report somatic RHOA mutations encoding a p.Gly17Val alteration in 68% of AITL samples. Remarkably, all cases with the mutation encoding p.Gly17Val also had TET2 mutations. The RHOA mutation encoding p.Gly17Val was specifically identified in tumor cells, whereas TET2 mutations were found in both tumor cells and non-tumor hematopoietic cells. RHOA encodes a small GTPase that regulates diverse biological processes. We demonstrated that the Gly17Val RHOA mutant did not bind GTP and also inhibited wild-type RHOA function. Our findings suggest that impaired RHOA function in cooperation with preceding loss of TET2 function contributes to AITL-specific pathogenesis.Entities:
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Year: 2014 PMID： 24413737 DOI： 10.1038/ng.2872
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307