001     127097
005     20240228140906.0
024 7 _ |a 10.1158/1078-0432.CCR-14-1324
|2 doi
024 7 _ |a pmid:25336695
|2 pmid
024 7 _ |a 1078-0432
|2 ISSN
024 7 _ |a 1557-3265
|2 ISSN
024 7 _ |a altmetric:2802351
|2 altmetric
037 _ _ |a DKFZ-2017-03123
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Merino, Diana M
|b 0
245 _ _ |a Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups.
260 _ _ |a Philadelphia, Pa. [u.a.]
|c 2015
|b AACR
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 312 - Functional and structural genomics (POF3-312)
|0 G:(DE-HGF)POF3-312
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650 _ 7 |a Neoplasm Proteins
|2 NLM Chemicals
650 _ 7 |a TP53 protein, human
|2 NLM Chemicals
650 _ 7 |a Tumor Suppressor Protein p53
|2 NLM Chemicals
700 1 _ |a Shlien, Adam
|b 1
700 1 _ |a Villani, Anita
|b 2
700 1 _ |a Pienkowska, Malgorzata
|b 3
700 1 _ |a Mack, Stephen
|b 4
700 1 _ |a Ramaswamy, Vijay
|b 5
700 1 _ |a Shih, David
|b 6
700 1 _ |a Tatevossian, Ruth
|b 7
700 1 _ |a Novokmet, Ana
|b 8
700 1 _ |a Choufani, Sanaa
|b 9
700 1 _ |a Dvir, Rina
|b 10
700 1 _ |a Ben-Arush, Myran
|b 11
700 1 _ |a Harris, Brent T
|b 12
700 1 _ |a Hwang, Eugene I
|b 13
700 1 _ |a Lulla, Rishi
|b 14
700 1 _ |a Pfister, Stefan
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700 1 _ |a Achatz, Maria Isabel
|b 16
700 1 _ |a Jabado, Nada
|b 17
700 1 _ |a Finlay, Jonathan L
|b 18
700 1 _ |a Weksberg, Rosanna
|b 19
700 1 _ |a Bouffet, Eric
|b 20
700 1 _ |a Hawkins, Cynthia
|b 21
700 1 _ |a Taylor, Michael D
|b 22
700 1 _ |a Tabori, Uri
|b 23
700 1 _ |a Ellison, David W
|b 24
700 1 _ |a Gilbertson, Richard J
|b 25
700 1 _ |a Malkin, David
|b 26
773 _ _ |a 10.1158/1078-0432.CCR-14-1324
|g Vol. 21, no. 1, p. 184 - 192
|0 PERI:(DE-600)2036787-9
|n 1
|p 184 - 192
|t Clinical cancer research
|v 21
|y 2015
|x 1557-3265
909 C O |o oai:inrepo02.dkfz.de:127097
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910 1 _ |a Deutsches Krebsforschungszentrum
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914 1 _ |y 2015
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Marc 21