Isocitrate dehydrogenase 1R132H mutation in microglia/macrophages in gliomas: indication of a significant role of microglia/macrophages in glial tumorigenesis.
Somatic mutation of Isocitrate dehydrogenase 1 (IDH1) at the locus of R132 (IDH1 (R132H)) occurs in > 70% of WHO grade II-III gliomas and secondary glioblastomas. To date it remains unknown whether the mutation is restricted to glial tumor cells. Microglial cells are the resident macrophages in the central nervous system. Tumor-infiltrating microglial cells/macrophages are major stromal cellular components of malignant gliomas and substantially contribute to the tumor mass. Differential identification of the IDH1 (R132H) mutant cellular components is of particular importance for understanding of the mutation-associated tumor biology. Here we discovered that a significant portion of CD68(+), Iba1(+), CX3CR1(+) microglial cells/macrophages also harbor the IDH1R132H mutation. The findings provide novel insights for understanding the mutation-associated tumor biology relevant to clinical applications as a predictive and/or prognostic marker or therapeutic target.
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands. p.zheng.1@erasmusmc.nl
Ping-Pin
PP
Zheng
Marcel
M
van der Weiden
Peter J
PJ
van der Spek
Arnaud J P E
AJ
Vincent
Johan M
JM
Kros
D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D011379:Prognosis
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human