Abstract：
:The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. Comparisons of differentially essential genes between Ras-dependent and -independent lines uncover synthetic lethal partners of oncogenic Ras. Screens in both human AML and engineered mouse pro-B cells converge on a surprisingly small number of genes in the Ras processing and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling. Our findings suggest general strategies for defining mammalian gene networks and synthetic lethal interactions by exploiting the natural genetic and epigenetic diversity of human cancer cells.
journal_name
Celljournal_title
Cellauthors
Wang T,Yu H,Hughes NW,Liu B,Kendirli A,Klein K,Chen WW,Lander ES,Sabatini DMdoi
10.1016/j.cell.2017.01.013subject
Has Abstractpub_date
2017-02-23 00:00:00pages
890-903.e15issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(17)30061-2journal_volume
168pub_type
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