dataset
posted on 2023-03-31, 01:46 authored by Colles Price, Stanley Gill, Zandra V. Ho, Shawn M. Davidson, Erin Merkel, James M. McFarland, Lisa Leung, Andrew Tang, Maria Kost-Alimova, Aviad Tsherniak, Oliver Jonas, Francisca Vazquez, William C. Hahn Supplementary Tables 1-6. Supplementary Table 1 contains a list of constructs used in this manuscript. Tab 2 with Supplementary table 2 is a list of all six-sigma genes we identified. Supplementary table 3 contains EGLN1 CRISPR Associations with mutations, gene expression, CRISPR dependencies and copy number. Supplementary table 4 contains EGLN1 RNAi Associations with mutations, gene expression, RNAi dependencies and copy number. Supplementary Table 5 contains all cell line information and annotations used for this manuscript. Supplementary Table 6 contains RNA sequence data from EGLN1 KO cells and EGLN1 WT cells.
Funding
NIH
NCI
the H.L. Synder Foundation
National Cancer Institute
Carlos Slim Foundation
History
ARTICLE ABSTRACT
We hypothesized that candidate dependencies for which there are small molecules that are either approved or in advanced development for a nononcology indication may represent potential therapeutic targets. To test this hypothesis, we performed genome-scale loss-of-function screens in hundreds of cancer cell lines. We found that knockout of EGLN1, which encodes prolyl hydroxylase domain-containing protein 2 (PHD2), reduced the proliferation of a subset of clear cell ovarian cancer cell lines in vitro. EGLN1-dependent cells exhibited sensitivity to the pan-EGLN inhibitor FG-4592. The response to FG-4592 was reversed by deletion of HIF1A, demonstrating that EGLN1 dependency was related to negative regulation of HIF1A. We also found that ovarian clear cell tumors susceptible to both genetic and pharmacologic inhibition of EGLN1 required intact HIF1A. Collectively, these observations identify EGLN1 as a cancer target with therapeutic potential.
These findings reveal a differential dependency of clear cell ovarian cancers on EGLN1, thus identifying EGLN1 as a potential therapeutic target in clear cell ovarian cancer patients.
