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

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.

• Content Type Journal Article
• Category Clinical Study
• Pages 1-9
• DOI 10.1007/s11060-012-0909-1
• Authors
  • Matthieu Talagas, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
  • Pascale Marcorelles, Service d'Anatomie Pathologique, CHRU Brest, Hôpital Morvan, Brest, France
  • Arnaud Uguen, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
  • Sylvia Redon, Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Brest, France
  • Isabelle Quintin-Roué, Service d'Anatomie Pathologique, CHRU Brest, Hôpital Morvan, Brest, France
  • Sebastian Costa, Service d'Anatomie Pathologique, CHRU Brest, Hôpital Morvan, Brest, France
  • Claude Férec, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
  • Frédéric Morel, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
  • Phong Dam Hieu, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France
  • Marc De Braekeleer, Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

http://www.springerlink.com/content/0407n55722505p3v/

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