title: Molecular classification of low-grade diffuse gliomas.
abstract: The current World Health Organization classification recognizes three histological types of grade II low-grade diffuse glioma (diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma). However, the diagnostic criteria, in particular for oligoastrocytoma, are highly subjective. The aim of our study was to establish genetic profiles for diffuse gliomas and to estimate their predictive impact. In this study, we screened 360 World Health Organization grade II gliomas for mutations in the IDH1, IDH2, and TP53 genes and for 1p/19q loss and correlated these with clinical outcome. Most tumors (86%) were characterized genetically by TP53 mutation plus IDH1/2 mutation (32%), 1p/19q loss plus IDH1/2 mutation (37%), or IDH1/2 mutation only (17%). TP53 mutations only or 1p/19q loss only was rare (2 and 3%, respectively). The median survival of patients with TP53 mutation ± IDH1/2 mutation was significantly shorter than that of patients with 1p/19q loss ± IDH1/2 mutation (51.8 months vs. 58.7 months, respectively; P = 0.0037). Multivariate analysis with adjustment for age and treatment confirmed these results (P = 0.0087) and also revealed that TP53 mutation is a significant prognostic marker for shorter survival (P = 0.0005) and 1p/19q loss for longer survival (P = 0.0002), while IDH1/2 mutations are not prognostic (P = 0.8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma.
authors.affiliation: International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Sumihito
authors.initials: S
authors.lastname: Nobusawa
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brokinkel
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
authors.forename: Karsten
authors.initials: K
authors.lastname: Wrede
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Anne
authors.initials: A
authors.lastname: Vital
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Robert
authors.initials: R
authors.lastname: Stawski
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Umberto
authors.initials: U
authors.lastname: De Girolami
authors.forename: Paul
authors.initials: P
authors.lastname: Kleihues
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000328:Adult; D017677:Age Distribution; D001932:Brain Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005787:Gene Frequency; D016158:Genes, p53; D005838:Genotype; D005910:Glioma / Q000145:classification* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009154:Mutation; D009367:Neoplasm Staging / Q000379:methods*
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human