Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

Adam M. Fontebasso, Margret Shirinian, Dong Anh Khuong-Quang, Denise Bechet, Tenzin Gayden, Marcel Kool, Nicolas De Jay, Karine Jacob, Noha Gerges, Barbara Hutter, Huriye Seker-Cin, Hendrik Witt, Alexandre Montpetit, Sébastien Brunet, Pierre Lepage, Geneviève Bourret, Almos Klekner, László Bognár, Peter Hauser, Miklós GaramiJean Pierre Farmer, Jose Luis Montes, Jeffrey Atkinson, Sally Lambert, Tony Kwan, Andrey Korshunov, Uri Tabori, V. Peter Collins, Steffen Albrecht, Damien Faury, Stefan M. Pfister, Werner Paulus, Martin Hasselblatt, David T.W. Jones, Nada Jabado

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting noncerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2), whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.

Original languageEnglish
Pages (from-to)31844-31856
Number of pages13
JournalOncotarget
Volume6
Issue number31
DOIs
Publication statusPublished - Jan 1 2015

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Keywords

  • Aneuploidy
  • BRAF
  • MDM2
  • PLK2
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Oncology

Cite this

Fontebasso, A. M., Shirinian, M., Khuong-Quang, D. A., Bechet, D., Gayden, T., Kool, M., De Jay, N., Jacob, K., Gerges, N., Hutter, B., Seker-Cin, H., Witt, H., Montpetit, A., Brunet, S., Lepage, P., Bourret, G., Klekner, A., Bognár, L., Hauser, P., ... Jabado, N. (2015). Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age. Oncotarget, 6(31), 31844-31856. https://doi.org/10.18632/oncotarget.5571