Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors

Pediatr Blood Cancer. 2014 Apr;61(4):593-600. doi: 10.1002/pbc.24833. Epub 2013 Nov 19.


Backgrounds: Intracranial germ cell tumors (GCTs) are rare and heterogeneous with very little is known about their pathogenesis and underlying genetic abnormalities.

Procedures: In order to identify candidate genes and pathways which are involved in the pathogenesis of these tumors, we have profiled 62 intracranial GCTs for DNA copy number alterations (CNAs) and loss of heterozygosity (LOH) by using single nucleotide polymorphism (SNP) array and quantitative real time PCR (qPCR).

Results: Initially 27 cases of tumor tissues with matched blood samples were fully analyzed by SNP microarray and qPCR. Statistical analysis using the genomic identification of significant targets in cancer (GISTIC) tool identified 10 regions of significant copy number gain and 11 regions of significant copy number loss. While overall pattern of genomic aberration was similar between germinoma and nongerminomatous germ cell tumors (NGGCTs), a few subtype-specific peak regions were identified. Analysis by SNP array and qPCR was replicated using an independent cohort of 35 cases.

Conclusions: Frequent aberrations of CCND2 (12p13) and RB1 (13q14) suggest that Cyclin/CDK-RB-E2F pathway might play a critical role in the pathogenesis of intracranial GCTs. Frequent gain of PRDM14 (8q13) implies that transcriptional regulation of primordial germ cell specification might be an important factor in the development of this tumor.

Keywords: DNA copy number; SNP microarray; genomic profiling; intracranial germ cell tumor; loss of heterozygosity.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations / genetics*
  • Female
  • Follow-Up Studies
  • Genome, Human*
  • Humans
  • Infant
  • Infant, Newborn
  • Loss of Heterozygosity*
  • Male
  • Mutation / genetics
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Young Adult


  • Biomarkers, Tumor