Gene amplification is a poor prognostic factor in anaplastic oligodendrogliomas

¹ Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 711, and Université Pierre et Marie Curie-Paris 6, Laboratoire Biologie des Interactions Neurone-Glie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France
² Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 711, and Université Pierre et Marie Curie-Paris 6, Laboratoire Biologie des Interactions Neurone-Glie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
³ Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 711, and Université Pierre et Marie Curie-Paris 6, Laboratoire Biologie des Interactions Neurone-Glie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Neuropathologie R. Escourolle, Paris, France

^* To whom correspondence should be addressed. E-mail: ahmed.idbaih{at}gmail.com.

	Abstract

Various gene amplifications have been observed in gliomas. Prognostic-genomic correlations testing simultaneously all these amplified genes have never been conducted in anaplastic oligodendrogliomas. A set of 38 genes that have been reported to be amplified in gliomas and investigated as the main targets of amplicons were studied in a series of 52 anaplastic oligodendrogliomas using bacterial artificial chromosome-array based comparative genomic hybridization and quantitative polymerase chain reaction. Among the 38 target genes, 15 were found to be amplified in at least one tumor. Overall, 27% of anaplastic oligodendrogliomas exhibited at least one gene amplification. The most frequently amplified genes were epidermal growth factor receptor (EGFR) and cyclin-dependent kinase 4/sarcoma amplified sequence (CDK4/SAS) in 17% and 8% of anaplastic oligodendrogliomas, respectively. Gene amplification and codeletion of chromosome arms 1p/19q were perfectly exclusive (p = 0.005). In uni- and multivariate analyses, gene amplification was a negative prognostic factor for progression-free survival and overall survival in anaplastic oligodendrogliomas, providing complementary information to the classic prognostic factors identified in anaplastic oligodendrogliomas (extent of surgery, KPS, and chromosome arms 1p/19q status).

Key Words: amplification, anaplastic, gene, oligodendroglioma, prognosis

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