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@ARTICLE{Merino:127097,
author = {D. M. Merino and A. Shlien and A. Villani and M. Pienkowska
and S. Mack and V. Ramaswamy and D. Shih and R. Tatevossian
and A. Novokmet and S. Choufani and R. Dvir and M. Ben-Arush
and B. T. Harris and E. I. Hwang and R. Lulla and S.
Pfister$^*$ and M. I. Achatz and N. Jabado and J. L. Finlay
and R. Weksberg and E. Bouffet and C. Hawkins and M. D.
Taylor and U. Tabori and D. W. Ellison and R. J. Gilbertson
and D. Malkin},
title = {{M}olecular characterization of choroid plexus tumors
reveals novel clinically relevant subgroups.},
journal = {Clinical cancer research},
volume = {21},
number = {1},
issn = {1557-3265},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2017-03123},
pages = {184 - 192},
year = {2015},
abstract = {To investigate molecular alterations in choroid plexus
tumors (CPT) using a genome-wide high-throughput approach to
identify diagnostic and prognostic signatures that will
refine tumor stratification and guide therapeutic
options.One hundred CPTs were obtained from a
multi-institutional tissue and clinical database.
Copy-number (CN), DNA methylation, and gene expression
signatures were assessed for 74, 36, and 40 samples,
respectively. Molecular subgroups were correlated with
clinical parameters and outcomes.Unique molecular signatures
distinguished choroid plexus carcinomas (CPC) from choroid
plexus papillomas (CPP) and atypical choroid plexus
papillomas (aCPP); however, no significantly distinct
molecular alterations between CPPs and aCPPs were observed.
Allele-specific CN analysis of CPCs revealed two novel
subgroups according to DNA content: hypodiploid and
hyperdiploid CPCs. Hyperdiploid CPCs exhibited recurrent
acquired uniparental disomy events. Somatic mutations in
TP53 were observed in $60\%$ of CPCs. Investigating the
number of mutated copies of p53 per sample revealed a
high-risk group of patients with CPC carrying two copies of
mutant p53, who exhibited poor 5-year event-free (EFS) and
overall survival (OS) compared with patients with CPC
carrying one copy of mutant p53 (OS: $14.3\%,$ $95\%$
confidence interval, $0.71\%-46.5\%$ vs. $66.7\%,$
$28.2\%-87.8\%,$ respectively, P = 0.04; EFS: $0\%$ vs.
$44.4\%,$ $13.6\%-71.9\%,$ respectively, P = 0.03). CPPs and
aCPPs exhibited favorable survival.Our data demonstrate that
differences in CN, gene expression, and DNA methylation
signatures distinguish CPCs from CPPs and aCPPs; however,
molecular similarities among the papillomas suggest that
these two histologic subgroups are indeed a single molecular
entity. A greater number of copies of mutated TP53 were
significantly associated to increased tumor aggressiveness
and a worse survival outcome in CPCs. Collectively, these
findings will facilitate stratified approaches to the
clinical management of CPTs.},
keywords = {Neoplasm Proteins (NLM Chemicals) / TP53 protein, human
(NLM Chemicals) / Tumor Suppressor Protein p53 (NLM
Chemicals)},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25336695},
doi = {10.1158/1078-0432.CCR-14-1324},
url = {https://inrepo02.dkfz.de/record/127097},
}