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Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma

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Abstract

Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis. Eighty-three percent of mutations detected in tumors were also observed in cell-free DNAs. During the disease course, mutations were detectable in cell-free DNAs in a refractory case, while they disappeared in a chemosensitive case. These data suggest that the disease-specific gene mutations serve as sensitive indicators for ctDNAs and may also be applicable for non-invasive monitoring of minimal residual diseases in AITL.

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research (KAKENHI: 16H02660 to S.C.; JP16K15497 to M.S.-Y.) from the Ministry of Education, Culture, Sports, and Science of Japan and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development, AMED. This work was also supported by research grants from the Daiichi Sankyo Foundation of Life Science to M.S.-Y. and The Uehara Memorial Foundation to S.C.

Authorship and disclosures

M.S.-Y., R.N.-M., D.K., and S.C. designed and performed research, analyzed data, and wrote the paper; K.H., T.N., T.K., N.K., Y.Y., N.O., Y.H., and A.S. contributed to the sample collection and attended the vital discussion.

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Author notes

  1. Mamiko Sakata-Yanagimoto and Rie Nakamoto-Matsubara equally contributed to this manuscript.

Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Mamiko Sakata-Yanagimoto, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa & Shigeru Chiba

  2. Department of Hematology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan

    Mamiko Sakata-Yanagimoto, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa & Shigeru Chiba

  3. Department of Hematology, Comprehensive Human Biosciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Rie Nakamoto-Matsubara, Daisuke Komori, Tran B. Nguyen & Keiichiro Hattori

  4. Department of Clinical Laboratory, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan

    Toru Nanmoku

  5. Department of Internal Medicine, Hitachi General Hospital, 2-1-1 Jonancho, Hitachi, Ibaraki, 317-0777, Japan

    Atsushi Shinagawa

Authors
  1. Mamiko Sakata-Yanagimoto
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  2. Rie Nakamoto-Matsubara
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Corresponding authors

Correspondence to Mamiko Sakata-Yanagimoto or Shigeru Chiba.

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All authors approved the final manuscript and have no financial conflicts of interest.

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Sakata-Yanagimoto, M., Nakamoto-Matsubara, R., Komori, D. et al. Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma. Ann Hematol 96, 1471–1475 (2017). https://doi.org/10.1007/s00277-017-3038-2

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  • DOI: https://doi.org/10.1007/s00277-017-3038-2

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