title: Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors.
abstract: BACKGROUND
  Intracranial germ cell tumors (GCTs) are rare and heterogeneous with very little is known about their pathogenesis and underlying genetic abnormalities.
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas.
authors.forename: Keita
authors.initials: K
authors.lastname: Terashima
authors.forename: Alexander
authors.initials: A
authors.lastname: Yu
authors.forename: Wing-Yuk T
authors.initials: WY
authors.lastname: Chow
authors.forename: Wei-chun J
authors.initials: WC
authors.lastname: Hsu
authors.forename: Peikai
authors.initials: P
authors.lastname: Chen
authors.forename: Stephen
authors.initials: S
authors.lastname: Wong
authors.forename: Yeung Sam
authors.initials: YS
authors.lastname: Hung
authors.forename: Tomonari
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Masao
authors.initials: M
authors.lastname: Matsutani
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakamura
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Allen
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.forename: Jack M
authors.initials: JM
authors.lastname: Su
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.forename: Hon-chiu E
authors.initials: HC
authors.lastname: Leung
authors.forename: Tsz-Kwong
authors.initials: TK
authors.lastname: Man
authors.forename: Ching C
authors.initials: CC
authors.lastname: Lau
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015894:Genome, Human; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation / Q000235:genetics; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA copy number; SNP microarray; genomic profiling; intracranial germ cell tumor; loss of heterozygosity