Gene expression profiling and subgroup identification of oligodendrogliomas.
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.
Huang
Hervé
H
International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, F-69372 Lyon Cedex 08, France.
Okamoto
Yoshikazu
Y
Yokoo
Hideaki
H
Heppner
Frank L
FL
Vital
Anne
A
Fevre-Montange
Michelle
M
Jouvet
Anne
A
Yonekawa
Yasuhiro
Y
Lazaridis
Emmanuel N
EN
Kleihues
Paul
P
Ohgaki
Hiroko
H
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