Integrated molecular analysis of adult T cell leukemia/lymphoma

Keisuke Kataoka; Yasunobu Nagata; Akira Kitanaka; Yuichi Shiraishi; Teppei Shimamura; Jun Ichirou Yasunaga; Yasushi Totoki; Kenichi Chiba; Aiko Sato-Otsubo; Genta Nagae; Ryohei Ishii; Satsuki Muto; Shinichi Kotani; Yosaku Watatani; June Takeda; Masashi Sanada; Hiroko Tanaka; Hiromichi Suzuki; Yusuke Sato; Yusuke Shiozawa; Tetsuichi Yoshizato; Kenichi Yoshida; Hideki Makishima; Masako Iwanaga; Guangyong Ma; Kisato Nosaka; Masakatsu Hishizawa; Hidehiro Itonaga; Yoshitaka Imaizumi; Wataru Munakata; Hideaki Ogasawara; Toshitaka Sato; Ken Sasai; Kenzo Muramoto; Marina Penova; Takahisa Kawaguchi; Hiromi Nakamura; Natsuko Hama; Kotaro Shide; Yoko Kubuki; Tomonori Hidaka; Takuro Kameda; Tsuyoshi Nakamaki; Ken Ishiyama; Shuichi Miyawaki; Sung Soo Yoon; Kensei Tobinai; Yasushi Miyazaki; Akifumi Takaori-Kondo; Fumihiko Matsuda; Kengo Takeuchi; Osamu Nureki; Hiroyuki Aburatani; Toshiki Watanabe; Tatsuhiro Shibata; Masao Matsuoka; Satoru Miyano; Kazuya Shimoda; Seishi Ogawa

doi:10.1038/ng.3415

Integrated molecular analysis of adult T cell leukemia/lymphoma

Keisuke Kataoka, Yasunobu Nagata, Akira Kitanaka, Yuichi Shiraishi, Teppei Shimamura, Jun Ichirou Yasunaga, Yasushi Totoki, Kenichi Chiba, Aiko Sato-Otsubo, Genta Nagae, Ryohei Ishii, Satsuki Muto, Shinichi Kotani, Yosaku Watatani, June Takeda, Masashi Sanada, Hiroko Tanaka, Hiromichi Suzuki, Yusuke Sato, Yusuke ShiozawaTetsuichi Yoshizato, Kenichi Yoshida, Hideki Makishima, Masako Iwanaga, Guangyong Ma, Kisato Nosaka, Masakatsu Hishizawa, Hidehiro Itonaga, Yoshitaka Imaizumi, Wataru Munakata, Hideaki Ogasawara, Toshitaka Sato, Ken Sasai, Kenzo Muramoto, Marina Penova, Takahisa Kawaguchi, Hiromi Nakamura, Natsuko Hama, Kotaro Shide, Yoko Kubuki, Tomonori Hidaka, Takuro Kameda, Tsuyoshi Nakamaki, Ken Ishiyama, Shuichi Miyawaki, Sung Soo Yoon, Kensei Tobinai, Yasushi Miyazaki, Akifumi Takaori-Kondo, Fumihiko Matsuda, Kengo Takeuchi, Osamu Nureki, Hiroyuki Aburatani, Toshiki Watanabe, Tatsuhiro Shibata, Masao Matsuoka, Satoru Miyano, Kazuya Shimoda, Seishi Ogawa

Research output: Contribution to journal › Article › peer-review

518 Citations (Scopus)

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- 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.

Original language	English
Pages (from-to)	1304-1315
Number of pages	12
Journal	Nature genetics
Volume	47
Issue number	11
DOIs	https://doi.org/10.1038/ng.3415
Publication status	Published - 2015 Nov 1
Externally published	Yes

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.3415

Cite this

Kataoka, K., Nagata, Y., Kitanaka, A., Shiraishi, Y., Shimamura, T., Yasunaga, J. I., 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., ... Ogawa, S. (2015). Integrated molecular analysis of adult T cell leukemia/lymphoma. Nature genetics, 47(11), 1304-1315. https://doi.org/10.1038/ng.3415

Kataoka, K, Nagata, Y, Kitanaka, A, Shiraishi, Y, Shimamura, T, Yasunaga, JI, 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 2015, 'Integrated molecular analysis of adult T cell leukemia/lymphoma', Nature genetics, vol. 47, no. 11, pp. 1304-1315. https://doi.org/10.1038/ng.3415

@article{a44a6135cb92408a92231a701450ff2a,

title = "Integrated molecular analysis of adult T cell leukemia/lymphoma",

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- 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.",

author = "Keisuke Kataoka and Yasunobu Nagata and Akira Kitanaka and Yuichi Shiraishi and Teppei Shimamura and Yasunaga, {Jun Ichirou} and Yasushi Totoki and Kenichi Chiba and Aiko Sato-Otsubo and Genta Nagae and Ryohei Ishii and Satsuki Muto and Shinichi Kotani and Yosaku Watatani and June Takeda and Masashi Sanada and Hiroko Tanaka and Hiromichi Suzuki and Yusuke Sato and Yusuke Shiozawa and Tetsuichi Yoshizato and Kenichi Yoshida and Hideki Makishima and Masako Iwanaga and Guangyong Ma and Kisato Nosaka and Masakatsu Hishizawa and Hidehiro Itonaga and Yoshitaka Imaizumi and Wataru Munakata and Hideaki Ogasawara and Toshitaka Sato and Ken Sasai and Kenzo Muramoto and Marina Penova and Takahisa Kawaguchi and Hiromi Nakamura and Natsuko Hama and Kotaro Shide and Yoko Kubuki and Tomonori Hidaka and Takuro Kameda and Tsuyoshi Nakamaki and Ken Ishiyama and Shuichi Miyawaki and Yoon, {Sung Soo} and Kensei Tobinai and Yasushi Miyazaki and Akifumi Takaori-Kondo and Fumihiko Matsuda and Kengo Takeuchi and Osamu Nureki and Hiroyuki Aburatani and Toshiki Watanabe and Tatsuhiro Shibata and Masao Matsuoka and Satoru Miyano and Kazuya Shimoda and Seishi Ogawa",

note = "Funding Information: We thank S. Sakaguchi for expert opinion and M. Sago, M. Nakamura, H. Higashi, Y. Ogino, Y. Mori and S. Baba for technical assistance. This work was supported by Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan and the Japanese Agency for Medical Research and Development (Health and Labour Sciences Research Expenses for Commission and Applied Research for Innovative Treatment of Cancer), Japanese Society for the Promotion of Science (JSPS) KAKENHI (22134006), National Cancer Center Research and Development Funds (26-A-6) and the Funding Program for World-Leading Innovative Research and Development on Science and Technology (FIRST). The National Cancer Center Biobank was supported by the National Cancer Center Research and Development Fund, Japan. This research used computational resources of the K computer provided by the RIKEN Advanced Institute for Computational Science through the HPCI System Research project (hp140230). Supercomputing resources were also provided by the Human Genome Center, the Institute of Medical Science, The University of Tokyo. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = nov,

day = "1",

doi = "10.1038/ng.3415",

language = "English",

volume = "47",

pages = "1304--1315",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Integrated molecular analysis of adult T cell leukemia/lymphoma

AU - Kataoka, Keisuke

AU - Nagata, Yasunobu

AU - Kitanaka, Akira

AU - Shiraishi, Yuichi

AU - Shimamura, Teppei

AU - Yasunaga, Jun Ichirou

AU - Totoki, Yasushi

AU - Chiba, Kenichi

AU - Sato-Otsubo, Aiko

AU - Nagae, Genta

AU - Ishii, Ryohei

AU - Muto, Satsuki

AU - Kotani, Shinichi

AU - Watatani, Yosaku

AU - Takeda, June

AU - Sanada, Masashi

AU - Tanaka, Hiroko

AU - Suzuki, Hiromichi

AU - Sato, Yusuke

AU - Shiozawa, Yusuke

AU - Yoshizato, Tetsuichi

AU - Yoshida, Kenichi

AU - Makishima, Hideki

AU - Iwanaga, Masako

AU - Ma, Guangyong

AU - Nosaka, Kisato

AU - Hishizawa, Masakatsu

AU - Itonaga, Hidehiro

AU - Imaizumi, Yoshitaka

AU - Munakata, Wataru

AU - Ogasawara, Hideaki

AU - Sato, Toshitaka

AU - Sasai, Ken

AU - Muramoto, Kenzo

AU - Penova, Marina

AU - Kawaguchi, Takahisa

AU - Nakamura, Hiromi

AU - Hama, Natsuko

AU - Shide, Kotaro

AU - Kubuki, Yoko

AU - Hidaka, Tomonori

AU - Kameda, Takuro

AU - Nakamaki, Tsuyoshi

AU - Ishiyama, Ken

AU - Miyawaki, Shuichi

AU - Yoon, Sung Soo

AU - Tobinai, Kensei

AU - Miyazaki, Yasushi

AU - Takaori-Kondo, Akifumi

AU - Matsuda, Fumihiko

AU - Takeuchi, Kengo

AU - Nureki, Osamu

AU - Aburatani, Hiroyuki

AU - Watanabe, Toshiki

AU - Shibata, Tatsuhiro

AU - Matsuoka, Masao

AU - Miyano, Satoru

AU - Shimoda, Kazuya

AU - Ogawa, Seishi

N1 - Funding Information: We thank S. Sakaguchi for expert opinion and M. Sago, M. Nakamura, H. Higashi, Y. Ogino, Y. Mori and S. Baba for technical assistance. This work was supported by Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan and the Japanese Agency for Medical Research and Development (Health and Labour Sciences Research Expenses for Commission and Applied Research for Innovative Treatment of Cancer), Japanese Society for the Promotion of Science (JSPS) KAKENHI (22134006), National Cancer Center Research and Development Funds (26-A-6) and the Funding Program for World-Leading Innovative Research and Development on Science and Technology (FIRST). The National Cancer Center Biobank was supported by the National Cancer Center Research and Development Fund, Japan. This research used computational resources of the K computer provided by the RIKEN Advanced Institute for Computational Science through the HPCI System Research project (hp140230). Supercomputing resources were also provided by the Human Genome Center, the Institute of Medical Science, The University of Tokyo. Publisher Copyright: © 2015 Nature America, Inc.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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- 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.

AB - 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- 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.

UR - http://www.scopus.com/inward/record.url?scp=84945344219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945344219&partnerID=8YFLogxK

U2 - 10.1038/ng.3415

DO - 10.1038/ng.3415

M3 - Article

C2 - 26437031

AN - SCOPUS:84945344219

SN - 1061-4036

VL - 47

SP - 1304

EP - 1315

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Integrated molecular analysis of adult T cell leukemia/lymphoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this