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

Keita Terashima; Alexander Yu; Wing Yuk T. Chow; Wei chun J. Hsu; Peikai Chen; Stephen T. Wong; Yeung Sam Hung; Tomonari Suzuki; Ryo Nishikawa; Masao Matsutani; Hideo Nakamura; Ho Keung Ng; Jeffrey C. Allen; Kenneth D. Aldape; Jack M. Su; Adekunle M. Adesina; Hon chiu E. Leung; Tsz Kwong Man; Ching C. Lau

doi:10.1002/pbc.24833

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

Keita Terashima, Alexander Yu, Wing Yuk T. Chow, Wei chun J. Hsu, Peikai Chen, Stephen T. Wong, Yeung Sam Hung, Tomonari Suzuki, Ryo Nishikawa, Masao Matsutani, Hideo Nakamura, Ho Keung Ng, Jeffrey C. Allen, Kenneth D. Aldape, Jack M. Su, Adekunle M. Adesina, Hon chiu E. Leung, Tsz Kwong Man, Ching C. Lau

Research output: Contribution to journal › Article

28 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	593-600
Number of pages	8
Journal	Pediatric Blood and Cancer
Volume	61
Issue number	4
DOIs	https://doi.org/10.1002/pbc.24833
State	Published - Apr 2014

Keywords

DNA copy number
Genomic profiling
Intracranial germ cell tumor
Loss of heterozygosity
SNP microarray

ASJC Scopus subject areas

Oncology
Pediatrics, Perinatology, and Child Health
Hematology

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Terashima, K., Yu, A., Chow, W. Y. T., Hsu, W. C. J., Chen, P., Wong, S. T., 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., & Lau, C. C. (2014). Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatric Blood and Cancer, 61(4), 593-600. https://doi.org/10.1002/pbc.24833

Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. / Terashima, Keita; Yu, Alexander; Chow, Wing Yuk T.; Hsu, Wei chun J.; Chen, Peikai; Wong, Stephen T.; Hung, Yeung Sam; Suzuki, Tomonari; Nishikawa, Ryo; Matsutani, Masao; Nakamura, Hideo; Ng, Ho Keung; Allen, Jeffrey C.; Aldape, Kenneth D.; Su, Jack M.; Adesina, Adekunle M.; Leung, Hon chiu E.; Man, Tsz Kwong; Lau, Ching C.

In: Pediatric Blood and Cancer, Vol. 61, No. 4, 04.2014, p. 593-600.

Research output: Contribution to journal › Article

Terashima, K, Yu, A, Chow, WYT, Hsu, WCJ, Chen, P, Wong, ST, Hung, YS, Suzuki, T, Nishikawa, R, Matsutani, M, Nakamura, H, Ng, HK, Allen, JC, Aldape, KD, Su, JM, Adesina, AM, Leung, HCE, Man, TK & Lau, CC 2014, 'Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors', Pediatric Blood and Cancer, vol. 61, no. 4, pp. 593-600. https://doi.org/10.1002/pbc.24833

Terashima, Keita ; Yu, Alexander ; Chow, Wing Yuk T. ; Hsu, Wei chun J. ; Chen, Peikai ; Wong, Stephen T. ; Hung, Yeung Sam ; Suzuki, Tomonari ; Nishikawa, Ryo ; Matsutani, Masao ; Nakamura, Hideo ; Ng, Ho Keung ; Allen, Jeffrey C. ; Aldape, Kenneth D. ; Su, Jack M. ; Adesina, Adekunle M. ; Leung, Hon chiu E. ; Man, Tsz Kwong ; Lau, Ching C. / Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. In: Pediatric Blood and Cancer. 2014 ; Vol. 61, No. 4. pp. 593-600.

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abstract = "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.",

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AU - Yu, Alexander

AU - Chow, Wing Yuk T.

AU - Hsu, Wei chun J.

AU - Chen, Peikai

AU - Wong, Stephen T.

AU - Hung, Yeung Sam

AU - Suzuki, Tomonari

AU - Nishikawa, Ryo

AU - Matsutani, Masao

AU - Nakamura, Hideo

AU - Ng, Ho Keung

AU - Allen, Jeffrey C.

AU - Aldape, Kenneth D.

AU - Su, Jack M.

AU - Adesina, Adekunle M.

AU - Leung, Hon chiu E.

AU - Man, Tsz Kwong

AU - Lau, Ching C.

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

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