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The landscape of cancer cell line metabolism

Li, Haoxin and Ning, Shaoyang and Apfel, Verena and Ghandi, Mahmoud and Kryukov, Gregory and Gopal, Shuba and Giannakis, Marios and Deik, Amy and Souza, Amanda and Pierce, Kerry and Keskula, Paula and Hernandez, Desiree and Ann, Julie and Shkoza, Dojna and Queiros De Almeida, Reinaldo and Tsherniak, Aviad and Weir, Barbara and Vazquez, Francisca and Hahn, William and Barretina, Jordi and Pagliarini, Raymond and Galli, Giorgio and Schreiber, Stuart and Clish, Clary and Sellers, William and Garraway, Levi (2019) The landscape of cancer cell line metabolism. Nature Medicine, 25 (5). pp. 850-860. ISSN 1546170X

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.

Item Type: Article
Date Deposited: 27 Aug 2019 00:45
Last Modified: 27 Aug 2019 00:45
URI: https://oak.novartis.com/id/eprint/34297

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