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@ARTICLE{Chudasama:131775,
author = {P. Chudasama$^*$ and S. S. Mughal$^*$ and M. A. Sanders and
D. Hübschmann$^*$ and I. Chung$^*$ and K. Deeg$^*$ and
S.-H. Wong$^*$ and S. Rabe$^*$ and M. Hlevnjak$^*$ and M.
Zapatka and A. Ernst$^*$ and K. Kleinheinz and M. Schlesner
and L. Sieverling$^*$ and B. Klink and E. Schröck$^*$ and
R. M. Hoogenboezem and B. Kasper and C. E. Heilig and G.
Egerer and S. Wolf$^*$ and C. von Kalle$^*$ and R. Eils$^*$
and A. Stenzinger$^*$ and W. Weichert$^*$ and H. Glimm$^*$
and S. Gröschel$^*$ and H.-G. Kopp and G. Omlor and B.
Lehner and S. Bauer$^*$ and S. Schimmack and A. Ulrich and
G. Mechtersheimer and K. Rippe and B. Brors and B. Hutter
and M. Renner and P. Hohenberger and C. Scholl$^*$ and S.
Fröhling$^*$},
title = {{I}ntegrative genomic and transcriptomic analysis of
leiomyosarcoma.},
journal = {Nature Communications},
volume = {9},
number = {1},
issn = {2041-1723},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2018-00072},
pages = {144},
year = {2018},
abstract = {Leiomyosarcoma (LMS) is an aggressive mesenchymal
malignancy with few therapeutic options. The mechanisms
underlying LMS development, including clinically actionable
genetic vulnerabilities, are largely unknown. Here we show,
using whole-exome and transcriptome sequencing, that LMS
tumors are characterized by substantial mutational
heterogeneity, near-universal inactivation of TP53 and RB1,
widespread DNA copy number alterations including
chromothripsis, and frequent whole-genome duplication.
Furthermore, we detect alternative telomere lengthening in
$78\%$ of cases and identify recurrent alterations in
telomere maintenance genes such as ATRX, RBL2, and SP100,
providing insight into the genetic basis of this mechanism.
Finally, most tumors display hallmarks of 'BRCAness',
including alterations in homologous recombination DNA repair
genes, multiple structural rearrangements, and enrichment of
specific mutational signatures, and cultured LMS cells are
sensitive towards olaparib and cisplatin. This comprehensive
study of LMS genomics has uncovered key biological features
that may inform future experimental research and enable the
design of novel therapies.},
cin = {G100 / G200 / B080 / B240 / B060 / L101 / L301 / W190 /
G240 / L701 / G250 / L801 / L401 / G102},
ddc = {500},
cid = {I:(DE-He78)G100-20160331 / I:(DE-He78)G200-20160331 /
I:(DE-He78)B080-20160331 / I:(DE-He78)B240-20160331 /
I:(DE-He78)B060-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)L301-20160331 / I:(DE-He78)W190-20160331 /
I:(DE-He78)G240-20160331 / I:(DE-He78)L701-20160331 /
I:(DE-He78)G250-20160331 / I:(DE-He78)L801-20160331 /
I:(DE-He78)L401-20160331 / I:(DE-He78)G102-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29321523},
pmc = {pmc:PMC5762758},
doi = {10.1038/s41467-017-02602-0},
url = {https://inrepo02.dkfz.de/record/131775},
}