Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q using array CGH

J Neurooncol. 2012 Sep;109(2):405-13. doi: 10.1007/s11060-012-0909-1. Epub 2012 Jul 24.

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.

MeSH terms

  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • Cell Cycle Proteins
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 19 / genetics*
  • Class II Phosphatidylinositol 3-Kinases
  • Cyclin-Dependent Kinase 4 / genetics
  • Cytidine Deaminase / genetics
  • Female
  • Gene Expression Profiling
  • Humans
  • In Situ Hybridization, Fluorescence
  • Loss of Heterozygosity*
  • Male
  • Minor Histocompatibility Antigens
  • Nuclear Proteins / genetics
  • Oligodendroglioma / diagnosis
  • Oligodendroglioma / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-mdm2 / genetics

Substances

  • Cell Cycle Proteins
  • MDM4 protein, human
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Class II Phosphatidylinositol 3-Kinases
  • PIK3C2B protein, human
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • APOBEC3B protein, human
  • Cytidine Deaminase