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Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified

Author

Listed:
  • Koen Debackere

    (Laboratory for Experimental Hematology, KU Leuven
    Center for Cancer Biology, VIB)

  • Lukas Marcelis

    (Translational Cell & Tissue Research, KU Leuven)

  • Sofie Demeyer

    (Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Marlies Vanden Bempt

    (Laboratory for Experimental Hematology, KU Leuven
    Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Nicole Mentens

    (Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Olga Gielen

    (Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Kris Jacobs

    (Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Michael Broux

    (Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Gregor Verhoef

    (Laboratory for Experimental Hematology, KU Leuven
    University Hospitals Leuven)

  • Lucienne Michaux

    (Center for Human Genetics, KU Leuven
    Center for Human Genetics, University Hospitals Leuven)

  • Carlos Graux

    (Mont-Godinne University Hospital)

  • Iwona Wlodarska

    (Center for Human Genetics, KU Leuven
    Center for Human Genetics, University Hospitals Leuven)

  • Philippe Gaulard

    (Département de Pathologie, Groupe Hospitalier Henri Mondor, AP-HP
    INSERM U955 and Université Paris-Est)

  • Laurence Leval

    (Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University)

  • Thomas Tousseyn

    (Translational Cell & Tissue Research, KU Leuven
    University Hospitals Leuven)

  • Jan Cools

    (Center for Cancer Biology, VIB
    Center for Human Genetics, KU Leuven)

  • Daan Dierickx

    (Laboratory for Experimental Hematology, KU Leuven
    University Hospitals Leuven)

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.

Suggested Citation

  • Koen Debackere & Lukas Marcelis & Sofie Demeyer & Marlies Vanden Bempt & Nicole Mentens & Olga Gielen & Kris Jacobs & Michael Broux & Gregor Verhoef & Lucienne Michaux & Carlos Graux & Iwona Wlodarska, 2021. "Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24037-4
    DOI: 10.1038/s41467-021-24037-4
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