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Genome‐wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors
Author(s) -
Terashima Keita,
Yu Alexander,
Chow WingYuk T.,
Hsu Weichun J.,
Chen Peikai,
Wong Stephen,
Hung Yeung Sam,
Suzuki Tomonari,
Nishikawa Ryo,
Matsutani Masao,
Nakamura Hideo,
Ng HoKeung,
Allen Jeffrey C.,
Aldape Kenneth D.,
Su Jack M.,
Adesina Adekunle M.,
Leung Honchiu E.,
Man TszKwong,
Lau Ching C.
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24833
Subject(s) - loss of heterozygosity , snp array , copy number variation , germ cell tumors , biology , single nucleotide polymorphism , pathogenesis , snp , copy number analysis , genetics , cancer research , comparative genomic hybridization , germinoma , medicine , gene , genome , genotype , immunology , allele , chemotherapy
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. Pediatr Blood Cancer 2014;61:593–600. © 2013 Wiley Periodicals, Inc.