論文 - 詳細
| RRC ID | 37916 |
|---|---|
| 著者 | Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, Totoki Y, Chiba K, Sato-Otsubo A, Nagae G, Ishii R, Muto S, Kotani S, Watatani Y, Takeda J, Sanada M, Tanaka H, Suzuki H, Sato Y, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Iwanaga M, Ma G, Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Ogasawara H, Sato T, Sasai K, Muramoto K, Penova M, Kawaguchi T, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Nakamaki T, Ishiyama K, Miyawaki S, Yoon SS, Tobinai K, Miyazaki Y, Takaori-Kondo A, Matsuda F, Takeuchi K, Nureki O, Aburatani H, Watanabe T, Shibata T, Matsuoka M, Miyano S, Shimoda K, Ogawa S. |
| タイトル | Integrated molecular analysis of adult T cell leukemia/lymphoma. |
| ジャーナル | Nat Genet |
| 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. |
| 巻・号 | 47(11) |
| ページ | 1304-15 |
| 公開日 | 2015-11-1 |
| DOI | 10.1038/ng.3415 |
| PII | ng.3415 |
| PMID | 26437031 |
| MeSH | Adult Amino Acid Sequence DNA Copy Number Variations DNA Methylation* Exome / genetics* Gene Products, tax / genetics Genome, Human / genetics* HEK293 Cells Host-Pathogen Interactions / genetics Human T-lymphotropic virus 1 / genetics Human T-lymphotropic virus 1 / physiology Humans Jurkat Cells Leukemia-Lymphoma, Adult T-Cell / genetics* Leukemia-Lymphoma, Adult T-Cell / virology Molecular Sequence Data Mutation Sequence Analysis, DNA / methods* Sequence Homology, Amino Acid Signal Transduction / genetics Survival Analysis T-Lymphocytes / metabolism T-Lymphocytes / virology Transcriptome / genetics* |
| IF | 27.605 |
| 引用数 | 286 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 62 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |