Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations

Hsei Wei Wang, Yu Hsuan Wu, Jui Yu Hsieh, Muh Lii Liang, Meng En Chao, Da Jung Liu, Ming Ta Hsu, Tai-Tong Wong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Intracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive drug and irradiation treatment regimens. The mechanisms underlying the differences in incidence and prognosis of the various GCT subgroups are unclear.Results: We identified a distinct mRNA profile correlating with GCT histological differentiation and prognosis, and also present in this study the first miRNA profile of pediatric primary intracranial GCTs. Most of the differentially expressed miRNAs were downregulated in germinomas, but miR-142-5p and miR-146a were upregulated. Genes responsible for self-renewal (such as POU5F1 (OCT4), NANOG and KLF4) and the immune response were abundant in germinomas, while genes associated with neuron differentiation, Wnt/β-catenin pathway, invasiveness and epithelial-mesenchymal transition (including SNAI2 (SLUG) and TWIST2) were abundant in NGMGCTs. Clear transcriptome segregation based on patient survival was observed, with malignant NGMGCTs being closest to embryonic stem cells. Chromosome copy number variations (CNVs) at cytobands 4q13.3-4q28.3 and 9p11.2-9q13 correlated with GCT malignancy and clinical risk. Six genes (BANK1, CXCL9, CXCL11, DDIT4L, ELOVL6 and HERC5) within 4q13.3-4q28.3 were more abundant in germinomas.Conclusions: Our results integrate molecular profiles with clinical observations and provide insights into the underlying mechanisms causing GCT malignancy. The genes, pathways and microRNAs identified have the potential to be novel therapeutic targets.

Original languageEnglish
Article number132
JournalBMC Genomics
Volume11
Issue number1
DOIs
Publication statusPublished - Feb 24 2010
Externally publishedYes

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Nervous System Neoplasms
Germ Cell and Embryonal Neoplasms
Central Nervous System
Chromosomes
Pediatrics
Germinoma
MicroRNAs
Neoplasms
Genes
Catenins
Wnt Signaling Pathway
Epithelial-Mesenchymal Transition
Teratoma
Embryonic Stem Cells
Transcriptome
Down-Regulation

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. / Wang, Hsei Wei; Wu, Yu Hsuan; Hsieh, Jui Yu; Liang, Muh Lii; Chao, Meng En; Liu, Da Jung; Hsu, Ming Ta; Wong, Tai-Tong.

In: BMC Genomics, Vol. 11, No. 1, 132, 24.02.2010.

Research output: Contribution to journalArticle

Wang, Hsei Wei ; Wu, Yu Hsuan ; Hsieh, Jui Yu ; Liang, Muh Lii ; Chao, Meng En ; Liu, Da Jung ; Hsu, Ming Ta ; Wong, Tai-Tong. / Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. In: BMC Genomics. 2010 ; Vol. 11, No. 1.
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AU - Wang, Hsei Wei

AU - Wu, Yu Hsuan

AU - Hsieh, Jui Yu

AU - Liang, Muh Lii

AU - Chao, Meng En

AU - Liu, Da Jung

AU - Hsu, Ming Ta

AU - Wong, Tai-Tong

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AB - Background: Intracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive drug and irradiation treatment regimens. The mechanisms underlying the differences in incidence and prognosis of the various GCT subgroups are unclear.Results: We identified a distinct mRNA profile correlating with GCT histological differentiation and prognosis, and also present in this study the first miRNA profile of pediatric primary intracranial GCTs. Most of the differentially expressed miRNAs were downregulated in germinomas, but miR-142-5p and miR-146a were upregulated. Genes responsible for self-renewal (such as POU5F1 (OCT4), NANOG and KLF4) and the immune response were abundant in germinomas, while genes associated with neuron differentiation, Wnt/β-catenin pathway, invasiveness and epithelial-mesenchymal transition (including SNAI2 (SLUG) and TWIST2) were abundant in NGMGCTs. Clear transcriptome segregation based on patient survival was observed, with malignant NGMGCTs being closest to embryonic stem cells. Chromosome copy number variations (CNVs) at cytobands 4q13.3-4q28.3 and 9p11.2-9q13 correlated with GCT malignancy and clinical risk. Six genes (BANK1, CXCL9, CXCL11, DDIT4L, ELOVL6 and HERC5) within 4q13.3-4q28.3 were more abundant in germinomas.Conclusions: Our results integrate molecular profiles with clinical observations and provide insights into the underlying mechanisms causing GCT malignancy. The genes, pathways and microRNAs identified have the potential to be novel therapeutic targets.

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