Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups

Clin Cancer Res. 2015 Jan 1;21(1):184-92. doi: 10.1158/1078-0432.CCR-14-1324. Epub 2014 Oct 21.


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.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Choroid Plexus Neoplasms / classification
  • Choroid Plexus Neoplasms / genetics*
  • Choroid Plexus Neoplasms / pathology
  • DNA Methylation / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Infant
  • Male
  • Mutation
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Staging
  • Prognosis*
  • Tumor Suppressor Protein p53 / genetics


  • Neoplasm Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53