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A novel recurrent EP300–ZNF384 gene fusion in B-cell precursor acute lymphoblastic leukemia

Leukemia volume 29, pages 2445–2448 (2015)Cite this article

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In pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), approximately three-quarters harbor well-characterized, clinically relevant chromosomal alterations, including hyperdiploidy, hypodiploidy, t(12;21) ETV6/RUNX1, t(1;19) E2A/PBX1, t(9;22) BCR/ABL1 and the rearrangement of MLL at 11q23, and they can facilitate diagnosis, risk stratification and targeted therapy.1, 2 In the remaining patients, however, major pathogenic or driver gene abnormalities and their association with the clinical outcome have yet to be fully clarified. As recent advanced genomic studies using next-generation sequencing have identified a number of novel fusion genes and stratified a high-risk subtype in BCP-ALL,3, 4, 5 unknown genetic alterations that constitute characteristic subgroups may still exist in the remaining patients. We therefore intended to investigate unknown fusion genes in BCP-ALL by using next-generation sequencing.

EP300 encodes the E1A-binding protein p300 (EP300), a transcriptional co-activator closely related to CREB-binding protein (CBP) and with the ability to interact with a wide spectrum of transcription factors and histone acetyltransferase activity.6 On the other hand, the zinc-finger protein 384 (ZNF384) gene encodes a transcription factor that regulates promoters of the extracellular matrix genes.7 Chromosomal translocations involving EP300 fused to either Monocytic leukemia zinc-finger protein (MOZ) or Mixed lineage leukemia (MLL) genes are associated with acute myeloid leukemia.8, 9 ZNF384 is known to be involved in ALL through fusion with the TET family gene, such as the Ewing sarcoma breakpoint region 1 (EWSR1) gene, TATA box binding protein-associated factor (TAF15) and transcription factor 3 (TCF3 or E2A).10, 11 Although the mutations of both EP300 and ZNF384 are known to be involved in the development of leukemia, this is the first report on the EP300–ZNF384 fusion gene.

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Acknowledgements

We thank K Itagaki, H Yagi, K Takeda and K Hayashi for their excellent data management and experimental assistance. We thank all members of the Committees of ALL and of Research and Diagnosis of the TCCSG. We also thank K Hayashi and LSI Medience Corporation for their excellent FISH analysis. This work was supported in part by a Health and Labour Sciences Research Grant (3rd-term comprehensive 10-year strategy for cancer control H22-011), the Grant of the National Center for Child Health and Development (26-20) and the Advanced research for medical products Mining Programme of the National Institute of Biomedical Innovation (NIBIO, 10-41, -42, -43, -44, -45). The above funding sources had no role in the collection, analysis or interpretation of the results, or in the writing of the manuscript and decision to submit it.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan

    Y Gocho, N Kiyokawa, T Ishibashi, H Ueno & K Terada

  2. Department of Pediatrics, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

    Y Gocho

  3. Division of Genetics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan

    H Ichikawa, H Sakamoto & T Yoshida

  4. Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan

    K Nakabayashi & K Hata

  5. Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan

    T Osumi & Y Shioda

  6. Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    T Ishibashi

  7. Department of Pediatrics, Japanese Red Cross Narita Hospital, Narita, Chiba, Japan

    K Terada & Y Noguchi

  8. Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science Setagaya-ku, Tokyo, Japan

    K Oboki

  9. Department of Pediatrics, Japanese Red Cross Musashino Hospital, Musashino, Tokyo, Japan

    M Imai

  10. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Y Arakawa & K Koh

  11. Department of Pediatrics, Toho University Omori Medical Center, Ota-ku, Tokyo, Japan

    Y Kojima & A Ohara

  12. Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan

    D Toyama

  13. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan

    K Matsumoto

  14. Department of Pediatrics, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    M Kato

  15. Department of Pediatrics, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    T Fukushima

  16. Department of Pediatrics, St. Luke's International Hospital, Chuo–ku, Tokyo, Japan

    A Manabe

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  1. Y Gocho
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Correspondence to N Kiyokawa.

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Gocho, Y., Kiyokawa, N., Ichikawa, H. et al. A novel recurrent EP300–ZNF384 gene fusion in B-cell precursor acute lymphoblastic leukemia. Leukemia 29, 2445–2448 (2015). https://doi.org/10.1038/leu.2015.111

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