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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·2015·Nature Genetics
DOI 10.1038/ng.3415
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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.

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Metadata

Authors
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., 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, S.-S., 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.
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2015-10-05
Volume
47
Issue
11
Pages
1304-1315
ISSN
  • 1061-4036
  • 1546-1718
DOI
10.1038/ng.3415
Cited by
794
References
11
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Integrated molecular analysis of adult T cell leukemia/lymphoma. https://app.cochat.ai/papers/10.1038/ng.3415
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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. https://doi.org/10.1038/ng.3415

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