title: Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q using array CGH.
abstract: Oligodendroglial tumors (ODTs) are primary tumors of the central nervous system that show recurrent codeletion of whole chromosome arms 1p and 19q. Non-1p/19q-deleted high-grade ODTs can present other genetic aberrations, CDKN2A deletion (9p21.3), EGFR amplification (7p11.2) and/or chromosome 10 loss, which are associated with a poor prognosis. The identification of these abnormalities allowed drafting a histo-molecular classification. The aim of this study was to precisely identify, using array CGH, the genomic hallmarks of these tumors, particularly those that are not deleted on 1p/19q. We studied 14 formalin-fixed paraffin-embedded high-grade ODTs using pangenomic oligonucleotide array CGH with an average resolution of 22.3 kb. The 1p/19q codeletion was found in five anaplastic oligodendrogliomas. The three genomic aberrations carrying a poor prognosis were found, most often associated, in five out of nine tumors not deleted on 1p/19q. In addition, four recurrent copy number alterations, involving genes that participate to cell growth and cycle, were found to be strongly associated in five tumors not deleted on 1p/19q: gain or amplification at 1q32.1 (MDM4, PIK3C2B genes), 12q14.1 (CDK4 gene), 12q14.3-q15 (MDM2 gene) and homozygous deletion at 22q13.1 (APOBEC3B gene). MDM2, MDM4, CDK4 and PIK3C2B are known for potentially being amplified or overexpressed in high-grade gliomas. However, the involvement of APOBEC3B, coding for mRNA edition enzyme, is described here for the first time. Our results show a strong association between these four alterations. Therefore, this can open a perspective for a novel subgroup in high-grade ODTs not deleted on 1p/19q.
authors: Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France.
authors: Matthieu
authors: M
authors: Talagas
authors: Pascale
authors: P
authors: Marcorelles
authors: Arnaud
authors: A
authors: Uguen
authors: Sylvia
authors: S
authors: Redon
authors: Isabelle
authors: I
authors: Quintin-Roué
authors: Sebastian
authors: S
authors: Costa
authors: Claude
authors: C
authors: Férec
authors: Frédéric
authors: F
authors: Morel
authors: Phong Dam
authors: PD
authors: Hieu
authors: Marc
authors: M
authors: De Braekeleer
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D018797:Cell Cycle Proteins; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D058541:Class II Phosphatidylinositol 3-Kinases; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D003564:Cytidine Deaminase / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000235:genetics; D009837:Oligodendroglioma / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D058541:Class II Phosphatidylinositol 3-Kinases; D051358:Cyclin-Dependent Kinase 4; D003564:Cytidine Deaminase; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; C482775:MDM4 protein, human; C497206:MDM2 protein, human; C502616:PIK3C2B protein, human; C495900:CDK4 protein, human; C495794:APOBEC3B protein, human