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Gene essentiality landscape and druggable oncogenic dependencies in herpesviral primary effusion lymphoma

Author

Listed:
  • Mark Manzano

    (Northwestern University)

  • Ajinkya Patil

    (Northwestern University)

  • Alexander Waldrop

    (Duke University)

  • Sandeep S. Dave

    (Duke University)

  • Amir Behdad

    (Northwestern University)

  • Eva Gottwein

    (Northwestern University)

Abstract

Primary effusion lymphoma (PEL) is caused by Kaposi’s sarcoma-associated herpesvirus. Our understanding of PEL is poor and therefore treatment strategies are lacking. To address this need, we conducted genome-wide CRISPR/Cas9 knockout screens in eight PEL cell lines. Integration with data from unrelated cancers identifies 210 genes as PEL-specific oncogenic dependencies. Genetic requirements of PEL cell lines are largely independent of Epstein-Barr virus co-infection. Genes of the NF-κB pathway are individually non-essential. Instead, we demonstrate requirements for IRF4 and MDM2. PEL cell lines depend on cellular cyclin D2 and c-FLIP despite expression of viral homologs. Moreover, PEL cell lines are addicted to high levels of MCL1 expression, which are also evident in PEL tumors. Strong dependencies on cyclin D2 and MCL1 render PEL cell lines highly sensitive to palbociclib and S63845. In summary, this work comprehensively identifies genetic dependencies in PEL cell lines and identifies novel strategies for therapeutic intervention.

Suggested Citation

  • Mark Manzano & Ajinkya Patil & Alexander Waldrop & Sandeep S. Dave & Amir Behdad & Eva Gottwein, 2018. "Gene essentiality landscape and druggable oncogenic dependencies in herpesviral primary effusion lymphoma," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05506-9
    DOI: 10.1038/s41467-018-05506-9
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    Cited by:

    1. Quanyuan Wan & Leah Tavakoli & Ting-Yu Wang & Andrew J. Tucker & Ruiting Zhou & Qizhi Liu & Shu Feng & Dongwon Choi & Zhiheng He & Michaela U. Gack & Jun Zhao, 2024. "Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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