Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature
of a major subset of primary human brain cancers. These mutations occur at a single amino
acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse
conversion of isocitrate to α-ketoglutarate. However, only a single copy of the gene is
mutated in tumours, raising the possibility that the mutations do not result in a simple loss of
function. Here we show that cancer-associated IDH1 mutations result in a new ability of the …

Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) are a common feature of most
gliomas and secondary glioblastomas, as well as approx 10% acute myeloid leukemias.
This event results in loss of the enzyme's ability to catalyze conversion of isocitrate to α-
ketoglutarate. However, these mutations are all heterozygous and occur at a single amino
acid residue of the IDH1 active site consistent with an enzymatic gain of function rather than
a simple loss of function. To test this hypothesis we characterized mutant IDH1 (IDH1m) …