TY - JOUR
T1 - Differential Activity of NADPH-Producing Dehydrogenases Renders Rodents Unsuitable Models to Study IDH1(R132) Mutation Effects in Human Glioblastoma
AU - Atai, Nadia A.
AU - Renkema-Mills, Nynke A.
AU - Bosman, Joost
AU - Schmidt, Nadja
AU - Rijkeboer, Denise
AU - Tigchelaar, Wikky
AU - Bosch, Klazien S.
AU - Troost, Dirk
AU - Jonker, Ard
AU - Bleeker, Fonnet E.
AU - Miletic, Hrvoje
AU - Bjerkvig, Rolf
AU - de Witt Hamer, Philip C.
AU - van Noorden, Cornelis J. F.
PY - 2011
Y1 - 2011
N2 - The somatic IDH1(R132) mutation in the isocitrate dehydrogenase 1 gene occurs in high frequency in glioma and in lower frequency in acute myeloid leukemia and thyroid cancer but not in other types of cancer. The mutation causes reduced NADPH production capacity in glioblastoma by 40% and is associated with prolonged patient survival. NADPH is a major reducing compound in cells that is essential for detoxification and may be involved in resistance of glioblastoma to treatment. IDH has never been considered important in NADPH production. Therefore, the authors investigated NADPH-producing dehydrogenases using in silico analysis of human cancer gene expression microarray data sets and metabolic mapping of human and rodent tissues to determine the role of IDH in total NADPH production. Expression of most NADPH-producing dehydrogenase genes was not elevated in 34 cancer data sets except for IDH1 in glioma and thyroid cancer, indicating an association with the IDH1 mutation. IDH activity was the main provider of NADPH in human normal brain and glioblastoma, but its role was modest in NADPH production in rodent brain and other tissues. It is concluded that rodents are a poor model to study consequences of the IDH1(R132) mutation in glioblastoma. (J Histochem Cytochem 59:489-503, 2011)
AB - The somatic IDH1(R132) mutation in the isocitrate dehydrogenase 1 gene occurs in high frequency in glioma and in lower frequency in acute myeloid leukemia and thyroid cancer but not in other types of cancer. The mutation causes reduced NADPH production capacity in glioblastoma by 40% and is associated with prolonged patient survival. NADPH is a major reducing compound in cells that is essential for detoxification and may be involved in resistance of glioblastoma to treatment. IDH has never been considered important in NADPH production. Therefore, the authors investigated NADPH-producing dehydrogenases using in silico analysis of human cancer gene expression microarray data sets and metabolic mapping of human and rodent tissues to determine the role of IDH in total NADPH production. Expression of most NADPH-producing dehydrogenase genes was not elevated in 34 cancer data sets except for IDH1 in glioma and thyroid cancer, indicating an association with the IDH1 mutation. IDH activity was the main provider of NADPH in human normal brain and glioblastoma, but its role was modest in NADPH production in rodent brain and other tissues. It is concluded that rodents are a poor model to study consequences of the IDH1(R132) mutation in glioblastoma. (J Histochem Cytochem 59:489-503, 2011)
U2 - https://doi.org/10.1369/0022155411400606
DO - https://doi.org/10.1369/0022155411400606
M3 - Article
C2 - 21527585
SN - 0022-1554
VL - 59
SP - 489
EP - 503
JO - Journal of Histochemistry and Cytochemistry
JF - Journal of Histochemistry and Cytochemistry
IS - 5
ER -