| Literature DB >> 31068703 |
Haoxin Li1,2, Shaoyang Ning3, Mahmoud Ghandi1, Gregory V Kryukov1, Shuba Gopal1, Amy Deik1, Amanda Souza1, Kerry Pierce1, Paula Keskula1, Desiree Hernandez1, Julie Ann4, Dojna Shkoza4, Verena Apfel5, Yilong Zou1, Francisca Vazquez1, Jordi Barretina4, Raymond A Pagliarini4, Giorgio G Galli5, David E Root1, William C Hahn1,2, Aviad Tsherniak1, Marios Giannakis1,2, Stuart L Schreiber1,6, Clary B Clish1, Levi A Garraway1,2, William R Sellers7,8.
Abstract
Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and associated dependencies remain uncommon. To further understand the metabolic diversity of cancer, we profiled 225 metabolites in 928 cell lines from more than 20 cancer types in the Cancer Cell Line Encyclopedia (CCLE) using liquid chromatography-mass spectrometry (LC-MS). This resource enables unbiased association analysis linking the cancer metabolome to genetic alterations, epigenetic features and gene dependencies. Additionally, by screening barcoded cell lines, we demonstrated that aberrant ASNS hypermethylation sensitizes subsets of gastric and hepatic cancers to asparaginase therapy. Finally, our analysis revealed distinct synthesis and secretion patterns of kynurenine, an immune-suppressive metabolite, in model cancer cell lines. Together, these findings and related methodology provide comprehensive resources that will help clarify the landscape of cancer metabolism.Entities:
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Year: 2019 PMID： 31068703 PMCID： PMC6629041 DOI： 10.1038/s41591-019-0404-8
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440