Molecular Characterization of Choroid Plexus Tumors Reveals Novel Clinically Relevant Subgroups

被引：61

作者：

Merino, Diana M. ^{[1
]}

Shlien, Adam ^{[1
]}

Villani, Anita ^{[1
]}

Pienkowska, Malgorzata ^{[1
]}

Mack, Stephen ^{[1
]}

Ramaswamy, Vijay ^{[1
]}

Shih, David ^{[1
]}

Tatevossian, Ruth ^{[2
]}

Novokmet, Ana ^{[1
]}

Choufani, Sanaa ^{[1
]}

Dvir, Rina ^{[3
]}

Ben-Arush, Myran ^{[4
]}

Harris, Brent T. ^{[5
]}

Hwang, Eugene I. ^{[6
]}

Lulla, Rishi ^{[7
]}

Pfister, Stefan M. ^{[8
]}

Achatz, Maria Isabel ^{[9
]}

Jabado, Nada ^{[10
]}

Finlay, Jonathan L. ^{[11
]}

Weksberg, Rosanna ^{[1
]}

Bouffet, Eric ^{[1
]}

Hawkins, Cynthia ^{[1
]}

Taylor, Michael D.

Tabori, Uri ^{[1
]}

Ellison, David W. ^{[2
]}

Gilbertson, Richard J. ^{[2
]}

Malkin, David ^{[1
]}

机构：

[1] Hosp Sick Children, Toronto, ON M5V 0A4, Canada

[2] St Jude Childrens Res Hosp, Memphis, TN 38105 USA

[3] Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel

[4] Rambam Hlth Care Campus, Haifa, Israel

[5] Georgetown Univ, Med Ctr, Washington, DC 20007 USA

[6] Childrens Natl Med Ctr, Washington, DC 20010 USA

[7] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA

[8] German Canc Res Ctr, Heidelberg, Germany

[9] AC Camargo Canc Ctr, Sao Paulo, Brazil

[10] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada

[11] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

来源：

CLINICAL CANCER RESEARCH | 2015年 / 21卷 / 01期

关键词：

PROGRESSION; EXPERIENCE;

D O I：

10.1158/1078-0432.CCR-14-1324

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: 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. Experimental Design: 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. Results: 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. Discussion: 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. (C) 2014 AACR.

引用

页码：184 / 192

页数：9

共 19 条

[1] Preoperative vincristine for an inoperable choroid plexus papilloma: a case discussion and review of the literature Case report [J].