title: IDH-Mutation Is a Weak Predictor of Long-Term Survival in Glioblastoma Patients.
abstract: BACKGROUND
  A very small proportion of patients diagnosed with glioblastoma (GBM) survive more than 3 years. Isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations define a small subgroup of GBM patients with favourable prognosis. However, it remains controversial whether long-term survivors (LTS) are found among those IDH1/2 mutated patients.
  
  
  METHODS
  We retrospectively analyzed 207 GBM patients followed at Lariboisière Hospital (Paris) between 2005 and 2010. Clinical parameters were obtained from medical records. Mutations of IDH1/2 were analyzed in these patients, by immunohistochemistry for the R132H mutation of IDH1 and by high-resolution melting-curve analysis, followed by Sanger sequencing for IDH1 and IDH2 exon 4 mutations. Mutation rates in LTS and non-LTS groups were compared by Chi square Pearson test.
  
  
  RESULTS
  Seventeen patients with survival >3 years were identified (8.2% of the total series). The median overall survival in long-term survivors was 4.6 years. Subgroup analysis found that the median age at diagnosis was significantly higher for non long-term survivors (non-LTS) compared to LTS (60 versus 51 years, p <0.03). The difference in the rate of IDH mutation between non-LTS and LTS was statistically not significant (1.16% versus 5.9%, p = 0.144). Among LTS, 10 out of 16 tumors presented a methylation of MGMT promoter.
  
  
  CONCLUSIONS
  This study confirms that long-term survival in GBM patients is if at all only weakly correlated to IDH-mutation.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Department of Neurosurgery, Paris, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Amelot
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), St-Louis Hospital, Department of Biochemistry, Molecular Oncology Unit, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: De Cremoux
authors.affiliation: Département de Biologie, Centre Eugène Marquis, CS 44229, Rue de la Bataille Flandres Dunkerque, 35042, Rennes Cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Department of pathology, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Polivka
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Department of pathology, Paris, France.
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), St-Louis Hospital, Department of Biochemistry, Molecular Oncology Unit, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lehmann-Che
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), St-Louis Hospital, Department of Biochemistry, Molecular Oncology Unit, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Françoise
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Avicennes Hospital, Department of Neurology, Bobigny, France.
authors.forename: Antoine F
authors.initials: AF
authors.lastname: Carpentier
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Department of Neurosurgery, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: George
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Department of Neurosurgery, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; IMNC, UMR 8165, Orsay, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mandonnet
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Lariboisière Hospital, Department of Neurosurgery, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Froelich
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D016009:Chi-Square Distribution; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors / Q000706:statistics & numerical data*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes