Ma Hsin-I, Kao Chung-Lan, Lee Yi-Yen, Chiou Guang-Yuh, Tai Lung-Kuo, Lu Kai-Hsi, Huang Chi-Shuan, Chen Yi-Wei, Chiou Shih-Hwa, Cheng Ing-Chan, Wong Tai-Tong
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Childs Nerv Syst. 2010 Mar;26(3):293-303. doi: 10.1007/s00381-009-1016-2. Epub 2009 Nov 10.
Atypical teratoid/rhabdoid tumor (AT/RT) and medulloblastoma (MB) are the most malignant primary brain tumors in early childhood. AT/RT is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. The biological features and clinical outcomes of AT/RT and MB are extremely different. In this study, we used microarray as a platform to distinguish these two tumors with the definitive diagnostic marker as well as the profiling of expression genes.
In order to clarify the pathogenesis and find the biological markers for AT/RT, we established a derivative AT/RT primary cell culture. The differential profiling between AT/RT and MB were analyzed by using microarray method.
With the use of the microarray method, we demonstrated that 15 genes were significantly changed (at least 5-fold in upregulation and 1/5-fold in downregulation) between AT/RT and MB in tissues and cell lines. The quantitative reverse transcription-polymerase chain reaction analyses further confirmed that mRNA expression levels of SERPINI1 and osteopontin were highly expressed in AT/RT cells and tissues than those in MB. Importantly, our microarray result suggested that AT/RT presents the stemness-like pattern and expression profiling of embryonic stem cells as well as high mRNA expressions of Oct-4, Nanog, Sox-2, and c-Myc.
Our study demonstrated the differential gene expression profiling between AT/RT and MB. Based on the microarray findings, AT/RTs present embryonic stem-like gene recapitulation and further provide novel insights into their underlying biology.
非典型畸胎样/横纹肌样瘤(AT/RT)和髓母细胞瘤(MB)是儿童早期最恶性的原发性脑肿瘤。AT/RT常被误诊为原始神经外胚层肿瘤/髓母细胞瘤。AT/RT和MB的生物学特征及临床结局截然不同。在本研究中,我们以基因芯片为平台,用明确的诊断标志物及表达基因谱来区分这两种肿瘤。
为阐明AT/RT的发病机制并寻找其生物学标志物,我们建立了一株AT/RT原代细胞培养物。采用基因芯片方法分析AT/RT和MB之间的差异表达谱。
运用基因芯片方法,我们证实在组织和细胞系中,AT/RT与MB之间有15个基因发生了显著变化(上调至少5倍,下调至1/5倍)。定量逆转录-聚合酶链反应分析进一步证实,丝氨酸蛋白酶抑制剂1(SERPINI1)和骨桥蛋白的mRNA表达水平在AT/RT细胞和组织中高于MB。重要的是,我们的基因芯片结果表明,AT/RT呈现出胚胎干细胞样的干性模式和表达谱,以及八聚体结合转录因子4(Oct-4)、Nanog、性别决定区Y框蛋白2(Sox-2)和原癌基因c-Myc的高mRNA表达。
我们的研究证明了AT/RT和MB之间存在差异基因表达谱。基于基因芯片的发现,AT/RT呈现出胚胎干细胞样基因重现性,为其潜在生物学特性提供了新的见解。