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

被引:131
作者
Ducray, Francois [1 ]
Idbaih, Ahmed [1 ]
de Reynies, Aurelien [4 ]
Bieche, Ivan [2 ]
Thillet, Joelle [1 ]
Mokhtari, Karima [1 ]
Lair, Severine [3 ]
Marie, Yannick [1 ]
Paris, Sophie [1 ]
Vidaud, Michel [2 ]
Hoang-Xuan, Khe [1 ]
Delattre, Olivier [3 ]
Delattre, Jean-Yves [1 ]
Sanson, Marc [1 ]
机构
[1] Univ Paris 06, Unite INSERM U711, F-75013 Paris, France
[2] Univ Paris 05, Fac Sci Pharmaceut & Biol, Unite INSERM U745, F-75270 Paris, France
[3] Ligue Natl Contre Canc, Serv Bioinformat, CIT, F-75006 Paris, France
[4] Ligue Natl Ctr Canc, Serv Bioinformat, Programme Cartes Identitie Tumeurs, F-75014 Paris, France
关键词
D O I
10.1186/1476-4598-7-41
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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.
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页数:17
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