title: Correlation between IDH1 gene mutation status and survival of patients treated for recurrent glioma.
abstract: Somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been frequently found in low-grade glioma and secondary glioblastoma and are associated with a significantly younger age at diagnosis and a superior overall survival. We investigated the IDH1 gene mutation status by nested PCR and denaturing gradient gel electrophoresis (DGGE) on DNA extracted from archival tumor blocks of 63 glioma patients who were treated following recurrence with the epidermal growth factor receptor (EGFR)-targeted blocking monoclonal antibody cetuximab, or the vascular endothelial growth factor (receptor) (VEGF(R))-targeted agents sunitinib malate and bevacizumab. In our study population, IDH1 mutation was significantly correlated with a longer overall survival (OS) from the time of initial diagnosis. Patients with IDH1 mutation also had a superior OS from the time of recurrence when treated with sunitinib or bevacizumab but a worse OS when treated with cetuximab. Our observations support the hypothesis that IDH1 mutation may correlate with the benefit from VEGF(R)- versus EGFR-targeted therapy at the time of recurrence in glioma patients.
authors.affiliation: Laboratory of Molecular Oncology and Department of Medical Oncology, Oncology center, UZ Brussels, University Hospital Brussels, Free University Brussels, Brussels, Belgium.
authors.forename: Shasha
authors.initials: S
authors.lastname: Lv
authors.forename: Erik
authors.initials: E
authors.lastname: Teugels
authors.forename: Jan
authors.initials: J
authors.lastname: Sadones
authors.forename: Erik
authors.initials: E
authors.lastname: Quartier
authors.forename: Mike
authors.initials: M
authors.lastname: Huylebrouck
authors.forename: Stephanie
authors.initials: S
authors.lastname: DU Four
authors.forename: Marie
authors.initials: M
authors.lastname: LE Mercier
authors.forename: Olivier
authors.initials: O
authors.lastname: DE Witte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.forename: Alex
authors.initials: A
authors.lastname: Michotte
authors.forename: Jacques
authors.initials: J
authors.lastname: DE Grève
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007521:Isocitrate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011758:Pyrroles / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D012008:Recurrence; D000077210:Sunitinib
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000068258:Bevacizumab; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; D000068818:Cetuximab; D000077210:Sunitinib