Journal Article

DKFZ-2017-04011

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Mack, S. C. ; Witt, H.DKFZ* ; Piro, R. M.DKFZ* ; Gu, L. ; Zuyderduyn, S. ; Stütz, A.DKFZ* ; Wang, X. ; Gallo, M. ; Garzia, L. ; Zayne, K. ; Zhang, X. ; Ramaswamy, V. ; Jäger, N.DKFZ* ; Jones, D.DKFZ* ; Sill, M.DKFZ* ; Pugh, T. J. ; Ryzhova, M.DKFZ* ; Wani, K. M. ; Shih, D. J. H. ; Head, R. ; Remke, M. ; Bailey, S. D. ; Zichner, T.DKFZ* ; Faria, C. C. ; Barszczyk, M. ; Stark, S.DKFZ* ; Seker-Cin, H.DKFZ* ; Hutter, S.DKFZ* ; Johann, P.DKFZ* ; Bender, S.DKFZ* ; Hovestadt, V.DKFZ* ; Tzaridis, T.DKFZ* ; Dubuc, A. M. ; Northcott, P. A.DKFZ* ; Peacock, J. ; Bertrand, K. C. ; Agnihotri, S. ; Cavalli, F. M. G. ; Clarke, I. ; Nethery-Brokx, K. ; Creasy, C. L. ; Verma, S. K. ; Koster, J. ; Wu, X. ; Yao, Y. ; Milde, T.DKFZ* ; Sin-Chan, P. ; Zuccaro, J. ; Lau, L. ; Pereira, S. ; Castelo-Branco, P. ; Hirst, M. ; Marra, M. A. ; Roberts, S. S. ; Fults, D. ; Massimi, L. ; Cho, Y. J. ; Van Meter, T. ; Grajkowska, W. ; Lach, B. ; Kulozik, A. E.DKFZ* ; von Deimling, A.DKFZ* ; Witt, O.DKFZ* ; Scherer, S. W. ; Fan, X. ; Muraszko, K. M. ; Kool, M.DKFZ* ; Pomeroy, S. L. ; Gupta, N. ; Phillips, J. ; Huang, A. ; Tabori, U. ; Hawkins, C. ; Malkin, D. ; Kongkham, P. N. ; Weiss, W. A. ; Jabado, N. ; Rutka, J. T. ; Bouffet, E. ; Korbel, J. O. ; Lupien, M. ; Aldape, K. D. ; Bader, G. D. ; Eils, R.DKFZ* ; Lichter, P.DKFZ* ; Dirks, P. B. ; Pfister, S. (Last author)DKFZ* ; Korshunov, A. (Last author)DKFZ* ; Taylor, M. D.

2014
Nature Publ. Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/nature13108

Abstract: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Keyword(s): Histones ; Polycomb Repressive Complex 2

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)
2. Molekulare Genetik (B060)
3. Theoretische Bioinformatik (B080)
4. Biostatistik (C060)
5. KKE Pädiatrische Onkologie (G340)
6. KKE Neuropathologie (G380)
7. DKTK Heidelberg (L101)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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