Molecular Characterization of Choroid Plexus Tumors Reveals Novel Clinically Relevant Subgroups
| Autor: | Stephen C. Mack, Ruth G. Tatevossian, Sanaa Choufani, Nada Jabado, Brent T. Harris, David Shih, Adam Shlien, Stefan M. Pfister, Richard J. Gilbertson, Eugene Hwang, Malgorzata Pienkowska, Michael D. Taylor, Anita Villani, Uri Tabori, Myran Ben-Arush, Ana Novokmet, Rina Dvir, Jonathan L. Finlay, Cynthia Hawkins, Vijay Ramaswamy, Diana M. Merino, Maria Isabel Achatz, Rishi Lulla, Eric Bouffet, Rosanna Weksberg, David Malkin, David W. Ellison |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Choroid Plexus Neoplasms Cancer Research Pathology medicine.medical_specialty Adolescent Somatic cell Biology medicine.disease_cause Disease-Free Survival Text mining Gene expression medicine Humans Child Neoplasm Staging Regulation of gene expression Mutation business.industry Infant DNA Methylation Prognosis medicine.disease Uniparental disomy Neoplasm Proteins Gene Expression Regulation Neoplastic Oncology Child Preschool DNA methylation Female Choroid plexus Tumor Suppressor Protein p53 business |
| Zdroj: | Clinical Cancer Research. 21:184-192 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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. Clin Cancer Res; 21(1); 184–92. ©2014 AACR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|