title: Gene expression profiling and subgroup identification of oligodendrogliomas.
abstract: The histological diagnosis of low-grade astrocytomas and oligodendrogliomas (WHO grade II) is often challenging, particularly in cases that show both astrocytic and oligodendroglial differentiation. We carried out gene expression profiling on 17 oligodendrogliomas (93% with LOH 1p and/or 19q) and 15 low-grade astrocytomas (71% with a TP53 mutation), using a cDNA array containing 1176 cancer-related genes. In oligodendrogliomas, 40 genes showed on average higher expression (at least a two-fold increase) than in astrocytomas, including DES, TDGF1, TGF-beta, GABA-BR1A, Histone H4, CDKN1A, PCDH43, Rho7 and Jun-D, while 39 genes were expressed at lower levels (at least a two-fold decrease), including JNK2, ITGB4, JNK3A2, RhoC, IFI-56K, AAD14 and EGFR. Immunohistochemistry revealed nuclear staining of Jun-D in oligodendrogliomas, in contrast to the immunoreactivity of cytoplasm and cell processes in low-grade astrocytomas. Partial least-squares analysis of the 79 genes at least two-fold differentially expressed between oligodendrogliomas and low-grade astrocytomas demonstrated perfect separation of oligodendrogliomas from low-grade astrocytomas and normal cerebral white matter. Clustering analysis based on the entire gene set divided the 17 subjects with oligodendrogliomas into two subgroups with significantly different survival (log-rank test, P=0.0305; survival to 5-years, 80 vs 0%, P=0.048). These results demonstrate that oligodendrogliomas and low-grade astrocytomas differ in their gene expression profiles, and that there are subgroups of oligodendroglioma with distinct expression profiles related to clinical outcome.
authors.affiliation: International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Huang
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yokoo
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Anne
authors.initials: A
authors.lastname: Vital
authors.forename: Michelle
authors.initials: M
authors.lastname: Fevre-Montange
authors.forename: Anne
authors.initials: A
authors.lastname: Jouvet
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: Emmanuel N
authors.initials: EN
authors.lastname: Lazaridis
authors.forename: Paul
authors.initials: P
authors.lastname: Kleihues
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009837:Oligodendroglioma / Q000145:classification / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis