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@ARTICLE{Dubois:180591,
author = {F. P. B. Dubois and O. Shapira and N. F. Greenwald and T.
Zack and J. Wala and J. W. Tsai and A. Crane and A. Baguette
and D. Hadjadj and A. S. Harutyunyan and K. H. Kumar and M.
Blattner-Johnson$^*$ and J. Vogelzang and C. Sousa and K. S.
Kang and C. Sinai and D. K. Wang and P. Khadka and K. Lewis
and L. Nguyen and H. Malkin and P. Ho and R. O'Rourke and S.
Zhang and R. Gold and D. Deng and J. Serrano and M. Snuderl
and C. Jones and K. D. Wright and S. N. Chi and J. Grill and
C. L. Kleinman and L. C. Goumnerova and N. Jabado and D.
Jones$^*$ and M. W. Kieran and K. L. Ligon and R. Beroukhim
and P. Bandopadhayay},
title = {{S}tructural variants shape driver combinations and
outcomes in pediatric high-grade glioma.},
journal = {Nature cancer},
volume = {3},
number = {8},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2022-01425},
pages = {994-1011},
year = {2022},
note = {2022 Aug;3(8):994-1011},
abstract = {We analyzed the contributions of structural variants (SVs)
to gliomagenesis across 179 pediatric high-grade gliomas
(pHGGs). The most recurrent SVs targeted MYC isoforms and
receptor tyrosine kinases (RTKs), including an SV amplifying
a MYC enhancer in $12\%$ of diffuse midline gliomas (DMG),
indicating an underappreciated role for MYC in pHGG. SV
signature analysis revealed that tumors with simple
signatures were TP53 wild type (TP53WT) but showed
alterations in TP53 pathway members PPM1D and MDM4. Complex
signatures were associated with direct aberrations in TP53,
CDKN2A and RB1 early in tumor evolution and with
later-occurring extrachromosomal amplicons. All pHGGs
exhibited at least one simple-SV signature, but complex-SV
signatures were primarily restricted to subsets of H3.3K27M
DMGs and hemispheric pHGGs. Importantly, DMGs with
complex-SV signatures were associated with shorter overall
survival independent of histone mutation and TP53 status.
These data provide insight into the impact of SVs on
gliomagenesis and the mechanisms that shape them.},
cin = {B360 / HD01},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35788723},
doi = {10.1038/s43018-022-00403-z},
url = {https://inrepo02.dkfz.de/record/180591},
}