Conflict of interest: Nothing to declare.
Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors
Article first published online: 19 NOV 2013
© 2013 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 61, Issue 4, pages 593–600, April 2014
How to Cite
Terashima, K., Yu, A., Chow, W.-Y. T., Hsu, W.-c. J., Chen, P., Wong, S., Hung, Y. S., Suzuki, T., Nishikawa, R., Matsutani, M., Nakamura, H., Ng, H.-K., Allen, J. C., Aldape, K. D., Su, J. M., Adesina, A. M., Leung, H.-c. E., Man, T.-K. and Lau, C. C. (2014), Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatr. Blood Cancer, 61: 593–600. doi: 10.1002/pbc.24833
- Issue published online: 6 FEB 2014
- Article first published online: 19 NOV 2013
- Manuscript Accepted: 1 OCT 2013
- Manuscript Received: 19 AUG 2013
- Children's Brain Tumor Foundation
- The Gillson Longenbaugh Foundation
- The Carl C. Anderson Sr. and Marie Jo Anderson Charitable Foundation
- Cancer Fighters of Houston
- Toyota-JMSA Scholarship
- St. Baldrick's Foundation
- DNA copy number;
- genomic profiling;
- intracranial germ cell tumor;
- loss of heterozygosity;
- SNP microarray
Intracranial germ cell tumors (GCTs) are rare and heterogeneous with very little is known about their pathogenesis and underlying genetic abnormalities.
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).
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.
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. Pediatr Blood Cancer 2014;61:593–600. © 2013 Wiley Periodicals, Inc.