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Gene amplification is a poor prognostic factor in anaplastic oligodendrogliomas

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 (A.I., E.C., Y.M., A.R., K.M., M.K., Y.E.H., C.C, S.P., B.B., F.L-D., J.T., M.S., K.H-X., J-Y.D.); Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France (A.I., F.L-D., M.S., K.H-X., J-Y.D.); AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Neuropathologie R. Escourolle, Paris, France (A.R., K.M., M.K.)

Address correspondence to Dr. Ahmed Idbaih, INSERM U711, Université Pierre et Marie Curie, Laboratoire Biologie des Interactions Neurone-Glie and Service de Neurologie Mazarin, Hôpital Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75013 Paris, France (ahmed.idbaih{at}gmail.com).

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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