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@ARTICLE{Okonechnikov:275588,
author = {K. Okonechnikov$^*$ and A. Camgöz$^*$ and O. Chapman and
S. Wani and D. E. Park and J.-M. Hübner$^*$ and A.
Chakraborty and M. Pagadala and R. Bump and S. Chandran and
K. Kraft and R. Acuna-Hidalgo and D. Reid and K. Sikkink and
M. Mauermann$^*$ and E. F. Juarez and A. Jenseit$^*$ and J.
T. Robinson and K. W. Pajtler$^*$ and T. Milde$^*$ and N.
Jäger$^*$ and P. Fiesel$^*$ and L. Morgan and S. Sridhar
and N. G. Coufal and M. Levy and D. Malicki and C. Hobbs and
S. Kingsmore and S. Nahas and M. Snuderl and J. Crawford and
R. J. Wechsler-Reya and T. B. Davidson and J. Cotter and G.
Michaiel and G. Fleischhack$^*$ and S. Mundlos and A.
Schmitt and H. Carter and K. A. Michealraj and S. A. Kumar
and M. D. Taylor and J. Rich and F. Buchholz$^*$ and J. P.
Mesirov and S. M. Pfister$^*$ and F. Ay and J. R. Dixon and
M. Kool$^*$ and L. Chavez},
title = {3{D} genome mapping identifies subgroup-specific chromosome
conformations and tumor-dependency genes in ependymoma.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-00799},
pages = {2300},
year = {2023},
note = {#EA:B062#LA:B062#},
abstract = {Ependymoma is a tumor of the brain or spinal cord. The two
most common and aggressive molecular groups of ependymoma
are the supratentorial ZFTA-fusion associated and the
posterior fossa ependymoma group A. In both groups, tumors
occur mainly in young children and frequently recur after
treatment. Although molecular mechanisms underlying these
diseases have recently been uncovered, they remain difficult
to target and innovative therapeutic approaches are urgently
needed. Here, we use genome-wide chromosome conformation
capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq,
as well as gene expression and DNA methylation analysis in
primary and relapsed ependymoma tumors, to identify
chromosomal conformations and regulatory mechanisms
associated with aberrant gene expression. In particular, we
observe the formation of new topologically associating
domains ('neo-TADs') caused by structural variants,
group-specific 3D chromatin loops, and the replacement of
CTCF insulators by DNA hyper-methylation. Through inhibition
experiments, we validate that genes implicated by these 3D
genome conformations are essential for the survival of
patient-derived ependymoma models in a group-specific
manner. Thus, this study extends our ability to reveal
tumor-dependency genes by 3D genome conformations even in
tumors that lack targetable genetic alterations.},
cin = {B062 / HD01 / B310 / B300 / ED01 / DD01},
ddc = {500},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B310-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)ED01-20160331 / I:(DE-He78)DD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37085539},
pmc = {pmc:PMC10121654},
doi = {10.1038/s41467-023-38044-0},
url = {https://inrepo02.dkfz.de/record/275588},
}