Integrated molecular analysis of adult T cell leukemia/lymphoma

被引：626

作者：

Kataoka, Keisuke ^{[1
]}

Nagata, Yasunobu ^{[1
]}

Kitanaka, Akira ^{[2
]}

Shiraishi, Yuichi ^{[3
]}

Shimamura, Teppei ^{[4
]}

Yasunaga, Jun-Ichirou ^{[5
]}

Totoki, Yasushi ^{[6
]}

Chiba, Kenichi ^{[3
]}

Sato-Otsubo, Aiko ^{[1
]}

Nagae, Genta ^{[7
]}

Ishii, Ryohei ^{[8
]}

Muto, Satsuki ^{[9
]}

Kotani, Shinichi ^{[1
]}

Watatani, Yosaku ^{[1
]}

Takeda, June ^{[1
]}

Sanada, Masashi ^{[1
,10
]}

Tanaka, Hiroko ^{[3
]}

Suzuki, Hiromichi ^{[1
]}

Sato, Yusuke ^{[1
]}

Shiozawa, Yusuke ^{[1
]}

Yoshizato, Tetsuichi ^{[1
]}

Yoshida, Kenichi ^{[1
]}

Makishima, Hideki ^{[1
]}

Iwanaga, Masako ^{[11
]}

Ma, Guangyong ^{[5
]}

Nosaka, Kisato ^{[12
]}

Hishizawa, Masakatsu ^{[13
]}

Itonaga, Hidehiro ^{[14
]}

Imaizumi, Yoshitaka ^{[15
]}

Munakata, Wataru ^{[16
]}

Ogasawara, Hideaki ^{[17
]}

Sato, Toshitaka ^{[17
]}

Sasai, Ken ^{[17
]}

Muramoto, Kenzo ^{[17
]}

Penova, Marina ^{[18
]}

Kawaguchi, Takahisa ^{[18
]}

Nakamura, Hiromi ^{[6
]}

Hama, Natsuko ^{[6
]}

Shide, Kotaro ^{[2
]}

Kubuki, Yoko ^{[2
]}

Hidaka, Tomonori ^{[2
]}

Kameda, Takuro ^{[2
]}

Nakamaki, Tsuyoshi ^{[19
]}

Ishiyama, Ken ^{[20
]}

Miyawaki, Shuichi ^{[21
]}

Yoon, Sung-Soo ^{[22
]}

Tobinai, Kensei

Miyazaki, Yasushi ^{[15
]}

Takaori-Kondo, Akifumi ^{[13
]}

Matsuda, Fumihiko ^{[18
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan

[2] Miyazaki Univ, Fac Med, Dept Gastroenterol & Hematol, Miyazaki, Japan

[3] Univ Tokyo, Ctr Human Genome, Lab DNA Informat Anal, Tokyo, Japan

[4] Nagoya Univ, Grad Sch Med, Ctr Neurol Dis & Canc, Div Syst Biol, Nagoya, Aichi 4648601, Japan

[5] Kyoto Univ, Inst Virus Res, Lab Virus Control, Kyoto 606, Japan

[6] Natl Canc Ctr, Res Inst, Div Canc Genom, Tokyo 104, Japan

[7] Univ Tokyo, Res Ctr Adv Sci & Technol, Genome Sci Div, Tokyo, Japan

[8] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Tokyo 113, Japan

[9] Univ Tokyo, Grad Sch Frontier Sci, Tokyo, Japan

[10] Nagoya Med Ctr, Clin Res Ctr, Dept Adv Diag, Nagoya, Aichi, Japan

[11] Nagasaki Univ, Grad Sch Biomed Sci, Dept Frontier Life Sci, Nagasaki 852, Japan

[12] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 860, Japan

[13] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan

[14] Sasebo City Gen Hosp, Dept Hematol, Sasebo, Japan

[15] Nagasaki Univ, Atom Bomb Dis & Hibakusya Med Unit, Dept Hematol, Atom Bomb Dis Inst, Nagasaki 852, Japan

[16] Natl Canc Ctr, Dept Hematol, Tokyo, Japan

[17] KAN Res Inst Inc, Kobe, Hyogo, Japan

[18] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[19] Showa Univ, Sch Med, Dept Med, Div Hematol, Tokyo 142, Japan

[20] Kanazawa Univ Hosp, Dept Hematol & Oncol, Kanazawa, Ishikawa, Japan

[21] Tokyo Metropolitan Otsuka Hosp, Dept Internal Med, Div Hematol, Tokyo, Japan

[22] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea

[23] Japanese Fdn Canc Res, Inst Canc, Pathol Project Mol Targets, Tokyo 170, Japan

[24] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med, Tokyo, Japan

来源：

NATURE GENETICS | 2015年 / 47卷 / 11期

关键词：

KAPPA-B ACTIVATION; VIRUS TYPE-I; PROTEIN-KINASE; MUTATIONS; CANCER; EXPRESSION; IDENTIFICATION; DYSFUNCTION; MECHANISMS; RECEPTORS;

D O I：

10.1038/ng.3415

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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-kappa B 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.

引用

页码：1304 / +

页数：15

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