Abstract #0329

IDH1 mutation down-regulates choline and ethanolamine metabolism in gliomas

Pavithra Viswanath¹, Jose Luis Izquierdo-Garcia¹, Joanna J Phillips², Russell O Pieper², and Sabrina M Ronen¹

¹Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

Aberrant choline and ethanolamine metabolism with elevated phosphocholine (PC) and phosphoethanolamine (PE) levels has emerged as a hallmark of cancer. Interestingly, PC and PE levels are reduced in gliomas with the isocitrate dehydrogenase 1 (IDH1) mutation relative to wild-type tumors. Here, we investigated the mechanism behind the reduction in PC and PE levels in genetically-engineered cells and tumor xenografts. Our results indicate that mutant IDH1 gliomas down-regulate the activities of choline kinase and ethanolamine kinase, the enzymes involved in PC and PE synthesis. Reduced PC and PE levels constitute unique metabolic biomarkers and potential therapeutic opportunities in mutant IDH1 gliomas.

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