IDH1R132H mutation causes a less aggressive phenotype and radiosensitizes human malignant glioma cells independent of the oxygenation status. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Kessler, Jacqueline; Güttler, Antje; Wichmann, Henri; Rot, Swetlana; Kappler, Matthias; Bache, Matthias; Vordermark, Dirk
• Is Part Of: Radiotherapy and oncology. Volume 116:Issue 3(2015:Sep.)
• Page Start: 381
• Page End: 387
• Publication Date: 2015-09
• Subjects: Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2015.08.007
• Languages: English
• ISSNs: 0167-8140

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st005">Abstract</title> <sec> <title id="st010">Background and purpose</title> <p id="sp0005">In malignant glioma the presence of the IDH1 mutation (IDH1<sup>R132H</sup>) 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.</p> </sec> <sec> <title id="st015">Material and methods</title> <p id="sp0010">We determined the influence of IDH1<sup>R132H</sup> mutant protein on proliferation and growth in 3D culture, migration, cell survival and radiosensitivity <italic>in vitro</italic> under normoxia (21% O<sub>2</sub>) and hypoxia (<1% O<sub>2</sub>) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1<sup>wt</sup>) and mutated IDH1 (IDH1<sup>R132H</sup>).</p> </sec> <sec> <title id="st020">Results</title> <p id="sp0015">Overexpression of IDH1<sup>R132H</sup> 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<sup>R132H</sup>-positive cells consistently demonstrated an increased radiosensitivity in human malignant glioma cells U-251MG (DMF<sub>10</sub>: 1.52, <italic>p</italic> < 0.01 and 1.42, <italic>p</italic> < 0.01), U-343MG (DMF<sub>10</sub>: 1.78, <italic>p</italic> < 0.01 and 1.75, <italic>p</italic> < 0.01) and LN-229 (DMF<sub>10</sub>: 1.41, <italic>p</italic> < 0.05 and 1.68, <italic>p</italic> < 0.01) under normoxia and hypoxia, respectively.</p> </sec> <sec> <title id="st025">Conclusion</title> <p id="sp0020">Our data indicate that IDH1<sup>R132H</sup> mutation causes both a less aggressive biological behavior and direct radiosensitization of human malignant glioma cells. Targeting IDH1 appears to be an attractive approach in combination with radiotherapy.</p> </sec> </abstract>