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Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia

Author

Listed:
  • Liqing Tian

    (St. Jude Children’s Research Hospital)

  • Ying Shao

    (St. Jude Children’s Research Hospital)

  • Stephanie Nance

    (St. Jude Children’s Research Hospital)

  • Jinjun Dang

    (St. Jude Children’s Research Hospital)

  • Beisi Xu

    (St. Jude Children’s Research Hospital)

  • Xiaotu Ma

    (St. Jude Children’s Research Hospital)

  • Yongjin Li

    (St. Jude Children’s Research Hospital)

  • Bensheng Ju

    (St. Jude Children’s Research Hospital)

  • Li Dong

    (St. Jude Children’s Research Hospital)

  • Scott Newman

    (St. Jude Children’s Research Hospital)

  • Xin Zhou

    (St. Jude Children’s Research Hospital)

  • Patrick Schreiner

    (St. Jude Children’s Research Hospital)

  • Elizabeth Tseng

    (Pacific Biosciences)

  • Ting Hon

    (Pacific Biosciences)

  • Meredith Ashby

    (Pacific Biosciences)

  • Chunliang Li

    (St. Jude Children’s Research Hospital)

  • John Easton

    (St. Jude Children’s Research Hospital)

  • Tanja A. Gruber

    (St. Jude Children’s Research Hospital)

  • Jinghui Zhang

    (St. Jude Children’s Research Hospital)

Abstract

IGH@ proto-oncogene translocation is a common oncogenic event in lymphoid lineage cancers such as B-ALL, lymphoma and multiple myeloma. Here, to investigate the interplay between IGH@ proto-oncogene translocation and IGH allelic exclusion, we perform long-read whole-genome and transcriptome sequencing along with epigenetic and 3D genome profiling of Nalm6, an IGH-DUX4 positive B-ALL cell line. We detect significant allelic imbalance on the wild-type over the IGH-DUX4 haplotype in expression and epigenetic data, showing IGH-DUX4 translocation occurs on the silenced IGH allele. In vitro, this reduces the oncogenic stress of DUX4 high-level expression. Moreover, patient samples of IGH-DUX4 B-ALL have similar expression profile and IGH breakpoints as Nalm6, suggesting a common mechanism to allow optimal dosage of non-toxic DUX4 expression.

Suggested Citation

  • Liqing Tian & Ying Shao & Stephanie Nance & Jinjun Dang & Beisi Xu & Xiaotu Ma & Yongjin Li & Bensheng Ju & Li Dong & Scott Newman & Xin Zhou & Patrick Schreiner & Elizabeth Tseng & Ting Hon & Meredit, 2019. "Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10637-8
    DOI: 10.1038/s41467-019-10637-8
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