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 journalArticle

250 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 languageEnglish
Pages (from-to)1304-1315
Number of pages12
JournalNature Genetics
Volume47
Issue number11
DOIs
StatePublished - 1 Nov 2015

Fingerprint

Adult T Cell Leukemia Lymphoma
Deltaretrovirus
T-Lymphocytes
Exome
Immunologic Monitoring
Mutation
Gene Fusion
Virus Diseases
T-Cell Antigen Receptor
Transcriptome
Methylation
Neoplasms
Genome
Therapeutics

Cite this

Kataoka, K., Nagata, Y., Kitanaka, A., Shiraishi, Y., Shimamura, T., Yasunaga, J. I., ... 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, Keisuke ; Nagata, Yasunobu ; Kitanaka, Akira ; Shiraishi, Yuichi ; Shimamura, Teppei ; Yasunaga, Jun Ichirou ; Totoki, Yasushi ; Chiba, Kenichi ; Sato-Otsubo, Aiko ; Nagae, Genta ; Ishii, Ryohei ; Muto, Satsuki ; Kotani, Shinichi ; Watatani, Yosaku ; Takeda, June ; Sanada, Masashi ; Tanaka, Hiroko ; Suzuki, Hiromichi ; Sato, Yusuke ; Shiozawa, Yusuke ; Yoshizato, Tetsuichi ; Yoshida, Kenichi ; Makishima, Hideki ; Iwanaga, Masako ; Ma, Guangyong ; Nosaka, Kisato ; Hishizawa, Masakatsu ; Itonaga, Hidehiro ; Imaizumi, Yoshitaka ; Munakata, Wataru ; Ogasawara, Hideaki ; Sato, Toshitaka ; Sasai, Ken ; Muramoto, Kenzo ; Penova, Marina ; Kawaguchi, Takahisa ; Nakamura, Hiromi ; Hama, Natsuko ; Shide, Kotaro ; Kubuki, Yoko ; Hidaka, Tomonori ; Kameda, Takuro ; Nakamaki, Tsuyoshi ; Ishiyama, Ken ; Miyawaki, Shuichi ; Yoon, Sung Soo ; Tobinai, Kensei ; Miyazaki, Yasushi ; Takaori-Kondo, Akifumi ; Matsuda, Fumihiko ; Takeuchi, Kengo ; Nureki, Osamu ; Aburatani, Hiroyuki ; Watanabe, Toshiki ; Shibata, Tatsuhiro ; Matsuoka, Masao ; Miyano, Satoru ; Shimoda, Kazuya ; Ogawa, Seishi. / Integrated molecular analysis of adult T cell leukemia/lymphoma. In: Nature Genetics. 2015 ; Vol. 47, No. 11. pp. 1304-1315.
@article{b9f9c3056a854bf489d4ed7e67c5117c,
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",
year = "2015",
month = "11",
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",

}

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

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

In: Nature Genetics, Vol. 47, No. 11, 01.11.2015, p. 1304-1315.

Research output: Contribution to journalArticle

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

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

U2 - 10.1038/ng.3415

DO - 10.1038/ng.3415

M3 - Article

C2 - 26437031

AN - SCOPUS:84945344219

VL - 47

SP - 1304

EP - 1315

JO - Nature genetics

JF - Nature genetics

SN - 1061-4036

IS - 11

ER -

Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga JI et al. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nature Genetics. 2015 Nov 1;47(11):1304-1315. https://doi.org/10.1038/ng.3415