title: IDH1(R132H) mutation increases U87 glioma cell sensitivity to radiation therapy in hypoxia.
abstract: OBJECTIVE
  IDH1 codon 132 mutation (mostly Arg132His) is frequently found in gliomas and is associated with longer survival. However, it is still unclear whether IDH1 mutation renders the cell more vulnerable to current treatment, radio- and chemotherapy.
  
  
  METHODS
  We transduced U87 with wild type IDH1 or IDH1 (R132H) expressing lentivirus and analyzed the radiosensitivity (dose ranging 0 to 10 Gy) under normoxia (20% O2) and moderate hypoxia (1% O2).
  
  
  RESULTS
  We observed that IDH1 (R132H) U87 cells grow faster in hypoxia and were more sensitive to radiotherapy (in terms of cell mortality and colony formation assay) compared to nontransduced U87 and IDH1 (wt) cells. This effect was not observed in normoxia.
  
  
  CONCLUSIONS
  These data suggest that IDH1 (R132H) mutation increases radiosensitivity in mild hypoxic conditions.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière (CRICM), UMR-S975, 75013 Paris, France ; INSERM, U 975, 75013 Paris, France ; CNRS, UMR 7225, 75013 Paris, France.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière (CRICM), UMR-S975, 75013 Paris, France ; INSERM, U 975, 75013 Paris, France ; CNRS, UMR 7225, 75013 Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Labussière
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Boulevard Henri Becquerel, BP 5229, 14074 Caen cedex, France ; Université de Caen Basse-Normandie, UMR 6301 ISTCT, 14000 Caen, France ; CEA, DSV/I2BM, UMR 6301 ISTCT, 14000 Caen, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Valable
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Boulevard Henri Becquerel, BP 5229, 14074 Caen cedex, France ; Université de Caen Basse-Normandie, UMR 6301 ISTCT, 14000 Caen, France ; CEA, DSV/I2BM, UMR 6301 ISTCT, 14000 Caen, France.
authors.forename: Elodie A
authors.initials: EA
authors.lastname: Pérès
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Boulevard Henri Becquerel, BP 5229, 14074 Caen cedex, France ; Université de Caen Basse-Normandie, UMR 6301 ISTCT, 14000 Caen, France ; CEA, DSV/I2BM, UMR 6301 ISTCT, 14000 Caen, France ; CHU de Caen, Service de Neurologie, Boulevard Côte de Nacre, 14000 Caen, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Guillamo
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Boulevard Henri Becquerel, BP 5229, 14074 Caen cedex, France ; Université de Caen Basse-Normandie, UMR 6301 ISTCT, 14000 Caen, France ; CEA, DSV/I2BM, UMR 6301 ISTCT, 14000 Caen, France.
authors.forename: Myriam
authors.identifier: 0000-0003-0778-3397
authors.initials: M
authors.lastname: Bernaudin
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière (CRICM), UMR-S975, 75013 Paris, France ; INSERM, U 975, 75013 Paris, France ; CNRS, UMR 7225, 75013 Paris, France ; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2, 75013 Paris, France ; Service de Neurologie 2, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris Cedex 13, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005910:Glioma / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011836:Radiation Tolerance / Q000528:radiation effects*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013997:Time Factors; D014161:Transduction, Genetic; D014410:Tumor Stem Cell Assay
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human