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Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas

Author

Listed:
  • Jay Daniels

    (Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine)

  • Peter G. Doukas

    (Northwestern University Feinberg School of Medicine)

  • Maria E. Martinez Escala

    (Northwestern University Feinberg School of Medicine)

  • Kimberly G. Ringbloom

    (Northwestern University Feinberg School of Medicine)

  • David J. H. Shih

    (The University of Texas MD Anderson Cancer Center)

  • Jingyi Yang

    (Northwestern University Feinberg School of Medicine)

  • Kyle Tegtmeyer

    (Northwestern University Feinberg School of Medicine)

  • Joonhee Park

    (Northwestern University Feinberg School of Medicine)

  • Jane J. Thomas

    (Northwestern University Feinberg School of Medicine)

  • Mehmet E. Selli

    (Northwestern University Feinberg School of Medicine)

  • Can Altunbulakli

    (Northwestern University Feinberg School of Medicine)

  • Ragul Gowthaman

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Samuel H. Mo

    (University of Illinois College of Medicine)

  • Balaji Jothishankar

    (University of Chicago Pritzker School of Medicine)

  • David R. Pease

    (Northwestern University Feinberg School of Medicine)

  • Barbara Pro

    (Northwestern University Feinberg School of Medicine)

  • Farah R. Abdulla

    (City of Hope Comprehensive Cancer Center)

  • Christopher Shea

    (University of Chicago Pritzker School of Medicine)

  • Nidhi Sahni

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine)

  • Alejandro A. Gru

    (University of Virginia Health System
    University of Virginia Health System)

  • Brian G. Pierce

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Abner Louissaint

    (Massachusetts General Hospital)

  • Joan Guitart

    (Northwestern University Feinberg School of Medicine)

  • Jaehyuk Choi

    (Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine
    Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine)

Abstract

Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Herein, we perform genome-wide DNA, RNA, and T cell receptor (TCR) sequencing on 29 cutaneous γδ lymphomas. We find that PCGDTLs are not uniformly derived from Vδ2 cells. Instead, the cell-of-origin depends on the tissue compartment from which the lymphomas are derived. Lymphomas arising from the outer layer of skin are derived from Vδ1 cells, the predominant γδ cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from Vδ2 cells, the predominant γδ T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for Vδ1 and Vδ2 lymphomas respectively. In addition, Vδ1 and Vδ2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways. Collectively, these findings suggest a paradigm for classifying, staging, and treating these diseases.

Suggested Citation

  • Jay Daniels & Peter G. Doukas & Maria E. Martinez Escala & Kimberly G. Ringbloom & David J. H. Shih & Jingyi Yang & Kyle Tegtmeyer & Joonhee Park & Jane J. Thomas & Mehmet E. Selli & Can Altunbulakli , 2020. "Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15572-7
    DOI: 10.1038/s41467-020-15572-7
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    Cited by:

    1. Stella Amanda & Tze King Tan & Jolynn Zu Lin Ong & Madelaine Skolastika Theardy & Regina Wan Ju Wong & Xiao Zi Huang & Muhammad Zulfaqar Ali & Yan Li & Zhiyuan Gong & Hiroshi Inagaki & Ee Yong Foo & B, 2022. "IRF4 drives clonal evolution and lineage choice in a zebrafish model of T-cell lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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