Pavithra Viswanath1, Jose Izquierdo-Garcia1, Larry Cai1, Joanna Phillips2, Russell Pieper2, and Sabrina M Ronen1
1Radiology, University of California San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California San Francisco, San Francisco, CA, United States
Abnormal choline metabolism with increased levels of
phosphocholine (PC) driven by overexpression of choline kinase α is considered
a hallmark of cancer. For the first time, we show that glioma cells with the
IDH1 mutation reprogram choline metabolism differently. Using 13C-MRS
to quantify [1,2-13C]-choline flux to PC in IDH1 mutant cells from
two genetically engineered glioma models, we show that reduced PC synthesis is characteristic
of mutant IDH1 cells. Furthermore, reduced PC synthesis is driven by down-regulated
choline kinase α expression. Our study points to unusual reprogramming of
choline metabolism in IDH1 mutant glioma cells, pointing to novel therapeutic
opportunities.
