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@ARTICLE{Mack:127989,
author = {S. C. Mack and H. Witt$^*$ and R. M. Piro$^*$ and L. Gu and
S. Zuyderduyn and A. Stütz$^*$ and X. Wang and M. Gallo and
L. Garzia and K. Zayne and X. Zhang and V. Ramaswamy and N.
Jäger$^*$ and D. Jones$^*$ and M. Sill$^*$ and T. J. Pugh
and M. Ryzhova$^*$ and K. M. Wani and D. J. H. Shih and R.
Head and M. Remke and S. D. Bailey and T. Zichner$^*$ and C.
C. Faria and M. Barszczyk and S. Stark$^*$ and H.
Seker-Cin$^*$ and S. Hutter$^*$ and P. Johann$^*$ and S.
Bender$^*$ and V. Hovestadt$^*$ and T. Tzaridis$^*$ and A.
M. Dubuc and P. A. Northcott$^*$ and J. Peacock and K. C.
Bertrand and S. Agnihotri and F. M. G. Cavalli and I. Clarke
and K. Nethery-Brokx and C. L. Creasy and S. K. Verma and J.
Koster and X. Wu and Y. Yao and T. Milde$^*$ and P. Sin-Chan
and J. Zuccaro and L. Lau and S. Pereira and P.
Castelo-Branco and M. Hirst and M. A. Marra and S. S.
Roberts and D. Fults and L. Massimi and Y. J. Cho and T. Van
Meter and W. Grajkowska and B. Lach and A. E. Kulozik$^*$
and A. von Deimling$^*$ and O. Witt$^*$ and S. W. Scherer
and X. Fan and K. M. Muraszko and M. Kool$^*$ and S. L.
Pomeroy and N. Gupta and J. Phillips and A. Huang and U.
Tabori and C. Hawkins and D. Malkin and P. N. Kongkham and
W. A. Weiss and N. Jabado and J. T. Rutka and E. Bouffet and
J. O. Korbel and M. Lupien and K. D. Aldape and G. D. Bader
and R. Eils$^*$ and P. Lichter$^*$ and P. B. Dirks and S.
Pfister$^*$ and A. Korshunov$^*$ and M. D. Taylor},
title = {{E}pigenomic alterations define lethal {CIMP}-positive
ependymomas of infancy.},
journal = {Nature},
volume = {506},
number = {7489},
issn = {1476-4687},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2017-04011},
pages = {445 - 450},
year = {2014},
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.},
keywords = {Histones (NLM Chemicals) / Polycomb Repressive Complex 2
(NLM Chemicals)},
cin = {B062 / B060 / B080 / C060 / G340 / G380 / L101},
ddc = {070},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)B080-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)G340-20160331 / I:(DE-He78)G380-20160331 /
I:(DE-He78)L101-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24553142},
pmc = {pmc:PMC4174313},
doi = {10.1038/nature13108},
url = {https://inrepo02.dkfz.de/record/127989},
}