| Literature DB >> 26437031 |
Keisuke Kataoka1, Yasunobu Nagata1, Akira Kitanaka2, Yuichi Shiraishi3, Teppei Shimamura4, Jun-Ichirou Yasunaga5, Yasushi Totoki6, Kenichi Chiba3, Aiko Sato-Otsubo1, Genta Nagae7, Ryohei Ishii8, Satsuki Muto9, Shinichi Kotani1, Yosaku Watatani1, June Takeda1, Masashi Sanada1,10, Hiroko Tanaka3, Hiromichi Suzuki1, Yusuke Sato1, Yusuke Shiozawa1, Tetsuichi Yoshizato1, Kenichi Yoshida1, Hideki Makishima1, Masako Iwanaga11, Guangyong Ma5, Kisato Nosaka12, Masakatsu Hishizawa13, Hidehiro Itonaga14, Yoshitaka Imaizumi15, Wataru Munakata16, Hideaki Ogasawara17, Toshitaka Sato17, Ken Sasai17, Kenzo Muramoto17, Marina Penova18, Takahisa Kawaguchi18, Hiromi Nakamura6, Natsuko Hama6, Kotaro Shide2, Yoko Kubuki2, Tomonori Hidaka2, Takuro Kameda2, Tsuyoshi Nakamaki19, Ken Ishiyama20, Shuichi Miyawaki21, Sung-Soo Yoon22, Kensei Tobinai16, Yasushi Miyazaki15, Akifumi Takaori-Kondo13, Fumihiko Matsuda18, Kengo Takeuchi23, Osamu Nureki8, Hiroyuki Aburatani7, Toshiki Watanabe9, Tatsuhiro Shibata6,24, Masao Matsuoka5, Satoru Miyano3, Kazuya Shimoda2, Seishi Ogawa1.
Abstract
Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV-1) infection. Here we describe an integrated molecular study in which we performed whole-genome, exome, transcriptome and targeted resequencing, as well as array-based copy number and methylation analyses, in a total of 426 ATL cases. The identified alterations overlap significantly with the HTLV-1 Tax interactome and are highly enriched for T cell receptor-NF-κB signaling, T cell trafficking and other T cell-related pathways as well as immunosurveillance. Other notable features include a predominance of activating mutations (in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7) and gene fusions (CTLA4-CD28 and ICOS-CD28). We also discovered frequent intragenic deletions involving IKZF2, CARD11 and TP73 and mutations in GATA3, HNRNPA2B1, GPR183, CSNK2A1, CSNK2B and CSNK1A1. Our findings not only provide unique insights into key molecules in T cell signaling but will also guide the development of new diagnostics and therapeutics in this intractable tumor.Entities:
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Year: 2015 PMID： 26437031 DOI： 10.1038/ng.3415
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330