title: Prognostic value of IDH1 mutations identified with PCR-RFLP assay in glioblastoma patients.
abstract: OBJECTIVE
  It has been shown that somatic missense mutations in codon 132 of the NADP+ dependent isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors including highly malignant glioblastoma (GBM). The aim of this study was to evaluate a PCR-restriction fragment length polymorphism (RFLP)-based method for missense mutation detection and to estimate the prognostic value of the two most frequent IDH1 codon 132 mutations, R132H and R132C, in patients with newly diagnosed GBM treated with radiation combined with temozolomide.
  
  
  METHODS
  DNA was extracted from formalin-fixed, paraffin-embedded tissue. The PCR-RFLP method was adapted to IDH1 codon 132 mutation screening. The mutation status was determined in a group of 58 patients.
  
  
  RESULTS
  We found R132H mutations in 14% of patients. No R132C mutation was found in this study. Median follow-up for living patients was 31 (range 17-51) months. Median progression-free survival in the group of patients with IDH1 mutation was 29 months compared with 10 months in the IDH1 wild-type group (p = 0.004; hazard ratio [HR] 3.09, 95% CI 1.25, 4.78). Median overall survival in the group with IDH1 mutation has not been reached, whereas in the group with wild-type IDH1 it was 19.5 months (p < 0.001; HR 4.76, 95% CI 1.22, 6.30). Three-year overall survival was 60% in the group with IDH1 mutation while in the wild-type IDH1 group it dropped to 29%. IDH1 mutations significantly correlated with younger age (p = 0.02).
  
  
  CONCLUSIONS
  Our results indicate that the IDH1 R132H mutation is a powerful prognostic marker in GBM treated with chemoradiation. The PCR-RFLP method allows for a fast, inexpensive, and sensitive mutation screening.
authors.affiliation: Department of Molecular Biology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. mbujko@coi.waw.pl
authors.forename: Mateusz
authors.initials: M
authors.lastname: Bujko
authors.forename: Paulina
authors.initials: P
authors.lastname: Kober
authors.forename: Ewa
authors.initials: E
authors.lastname: Matyja
authors.forename: Paweł
authors.initials: P
authors.lastname: Nauman
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dyttus-Cebulok
authors.forename: Beata
authors.initials: B
authors.lastname: Czeremszyńska
authors.forename: Wiesław
authors.initials: W
authors.lastname: Bonicki
authors.forename: Janusz A
authors.initials: JA
authors.lastname: Siedlecki
mesh_terms: D000328:Adult; D000368:Aged; D001681:Biological Assay / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human