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

BMC Genomics

Research Article

Da-Jung Liu¹  Tai-Tong Wong¹  Meng-En Chao¹  Ming-Ta Hsu²  Jui-Yu Hsieh³  Yu-Hsuan Wu³  Hsei-Wei Wang⁴  Muh-Lii Liang⁵ 

[1] Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan;School of Life Sciences, Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan;VGH Yang-Ming Genome Research Center, National Yang-Ming University, Taipei, Taiwan;School of Life Sciences, Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan;School of Life Sciences, Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan;School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;VGH Yang-Ming Genome Research Center, National Yang-Ming University, Taipei, Taiwan;Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan;

关键词: Teratoma;    Seminoma;    Germinomas;    Mature Teratoma;    Immature Teratoma;   

DOI  :  10.1186/1471-2164-11-132

 received in 2009-09-25, accepted in 2010-02-24,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundIntracranial 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Wang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.