Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile.
BACKGROUND
In high grade gliomas, 1p19q codeletion and EGFR amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with EGFR amplification, identified by CGH-array.


RESULTS
The two groups of gliomas exhibited very different gene expression profiles and were consistently distinguished by unsupervised clustering analysis. One of the most striking differences was the expression of normal brain genes by oligodendrogliomas with 1p19q codeletion. These gliomas harbored a gene expression profile that partially resembled the gene expression of normal brain samples, whereas gliomas with EGFR amplification expressed many genes in common with glioblastoma cancer stem cells. The differences between the two types of gliomas and the expression of neuronal genes in gliomas with 1p19q codeletion were both validated in an independent series of 16 gliomas using real-time RT-PCR with a set of 22 genes differentiating the two groups of gliomas (AKR1C3, ATOH8, BMP2, C20orf42, CCNB1, CDK2, CHI3L1, CTTNBP2, DCX, EGFR, GALNT13, GBP1, IGFBP2, IQGAP1, L1CAM, NCAM1, NOG, OLIG2, PDPN, PLAT, POSTN, RNF135). Immunohistochemical study of the most differentially expressed neuronal gene, alpha-internexin, clearly differentiated the two groups of gliomas, with 1p19q codeletion gliomas showing specific staining in tumor cells.


CONCLUSIONS
These findings provide evidence for neuronal differentiation in oligodendrogliomas with 1p19q codeletion and support the hypothesis that the cell of origin for gliomas with 1p19q codeletion could be a bi-potential progenitor cell, able to give rise to both neurons and oligodendrocytes.
Ducray
François
F
Unité INSERM U711, Université Paris VI, 47-83 Boulevard de l'Hôpital, 75013 Paris, France. francoisducray@yahoo.fr
Idbaih
Ahmed
A
de Reyniès
Aurélien
A
Bièche
Ivan
I
Thillet
Joëlle
J
Mokhtari
Karima
K
Lair
Séverine
S
Marie
Yannick
Y
Paris
Sophie
S
Vidaud
Michel
M
Hoang-Xuan
Khê
K
Delattre
Olivier
O
Delattre
Jean-Yves
JY
Sanson
Marc
M
D002872:Chromosome Deletion; D016000:Cluster Analysis; D066246:ErbB Receptors / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007381:Intermediate Filament Proteins; C046643:alpha-internexin; D066246:ErbB Receptors