Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile

作者：François Ducray, Ahmed Idbaïh, Aurélien de Reyniès, Ivan Bièche, Joëlle Thillet, Karima Mokhtari, Séverine Lair, Yannick Marie, Sophie Paris, Michel Vidaud, Khê Hoang‐Xuan, Olivier Delattre, Jean‐Yves Delattre, Marc Sanson · 发表于：Molecular Cancer · 年份：2008 · DOI：10.1186/1476-4598-7-41 · 被引用次数：171 · 研究领域：Glioma Diagnosis and Treatment、Neuroblastoma Research and Treatments、Neurofibromatosis and Schwannoma Cases

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. CONCLUSION: These findings provide evidence f...