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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Manzano M,Patil A,Waldrop A,Dave SS,Behdad A,Gottwein E

doi

10.1038/s41467-018-05506-9

subject

Has Abstract

pub_date

2018-08-15 00:00:00

pages

3263

issue

1

issn

2041-1723

pii

10.1038/s41467-018-05506-9

journal_volume

9

pub_type

杂志文章

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