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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