IDH1(R132H) mutation causes a less aggressive phenotype and radiosensitizes human malignant glioma cells independent of the oxygenation status

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Jacqueline KesslerDirk Vordermark

Abstract

In malignant glioma the presence of the IDH1 mutation (IDH1(R132H)) is associated with better clinical outcome. However, it is unclear whether IDH1 mutation is associated with a less aggressive phenotype or directly linked to increased sensitivity to radiotherapy. We determined the influence of IDH1(R132H) mutant protein on proliferation and growth in 3D culture, migration, cell survival and radiosensitivity in vitro under normoxia (21% O2) and hypoxia (<1% O2) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1(wt)) and mutated IDH1 (IDH1(R132H)). Overexpression of IDH1(R132H) in glioma cells resulted in slightly decreased cell proliferation, considerably reduced cell migration and caused differences in growth properties in 3D spheroid cultures. Furthermore, IDH1(R132H)-positive cells consistently demonstrated an increased radiosensitivity in human malignant glioma cells U-251MG (DMF10: 1.52, p<0.01 and 1.42, p<0.01), U-343MG (DMF10: 1.78, p<0.01 and 1.75, p<0.01) and LN-229 (DMF10: 1.41, p<0.05 and 1.68, p<0.01) under normoxia and hypoxia, respectively. Our data indicate that IDH1(R132H) mutation causes both a less aggressive biological behavior and direct r...Continue Reading

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Citations

Sep 20, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·H Peter Rodemann, Stephan Bodis
Feb 11, 2016·The International Journal of Biochemistry & Cell Biology·Daming CuiLiang Gao
Sep 21, 2017·International Journal of Molecular Sciences·Tim HohmannFaramarz Dehghani
Jun 4, 2019·International Journal of Molecular Sciences·Geon-Hee KimJi-Hong Lim
Feb 15, 2019·Science Translational Medicine·Felipe J NúñezMaria G Castro
Sep 8, 2016·Journal of Neuro-oncology·Oliver SchnellMaximilian Niyazi
Dec 21, 2017·AJR. American Journal of Roentgenology·Javier E Villanueva-MeyerSoonmee Cha
Feb 25, 2017·PloS One·Rahimsan K RamachandranBjarne W Kristensen

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