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Abstract #0840

Glutamatergic production of 2HG in IDH1-mutant tumor cells is retained by glutamate import in glutamine-free medium

Tom Peeters1, Vincent Breukels1, Krissie Lenting2, Sanne van Lith2, Arno van Rooij3, Remco Molenaar4, William Leenders2, and Arend Heerschap1

1Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, Netherlands, 2Pathology, Radboud university medical center, Nijmegen, Netherlands, 3Laboratory Medicine, Radboud university medical center, Nijmegen, Netherlands, 4Cell Biology and Histology, Academic Medical Center, Amsterdam, Netherlands

This study demonstrates that in IDH1-mutant tumor cells the pool of oncometabolite 2HG is predominantly replenished by αKG precursors glutamine and glutamate, and to a lesser extent by glucose-derived metabolites. Furthermore, we show that 2HG production is not significantly decreased when total the pool of glutamine and glutamate drops, which occurs upon substitution of glutamine by glutamate in the culture medium.

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