Molecular Pathological Analysis of the Differences in Biological Malignancy between S;inal and Intracranial Ependymomas

本项目的目的是揭示脊髓室管膜瘤和颅内室管膜瘤之间的分子病理学差异，它们表现出不同的生物学恶性1)我们建立了一种基于酵母的终止密码子检测截断型突变的方法，以分析室管膜瘤(AM)的分子病理学。我们开发了一个由1300个基因组成的原始DNA阵列。3)对8例脊椎室管膜瘤和8例颅内室管膜瘤进行了DNA芯片分析，得到了脊室管膜瘤和颅内室管膜瘤的几个特征基因(H-ras、M-ras、NCAM、ICAM-2、PDGFR-α、FGFR-3、p19INK4d)和颅内室管膜瘤(VEGF、p57Kip2、MIP3pha、MDM2、Cyclin D3、TGFbeta2)的特征基因。4)通过模式分类算法，包括聚类分析和支持向量机，我们发现这些表达谱可以很好地区分脊髓和颅内室管膜瘤我们发现，使用支持向量机对两个室管膜瘤实体进行STAT1和MIP-3α分类效果最好。我们现在正在分析这些分子在室管膜瘤中的生物学意义。

The Aim of this project is to disclose molecular pathological differences between spinal cord ependymomas and intracranial ependymomas, which show different biological malignancies.1) We developed a yeast-based stop codon assay to detect truncating type mutations, in order to analyse molecular pathology in ependymomas (Am. J. Pathol.)2) We developed an original DNA array consisting of 1300 genes. We analyzed 119 cancer cell lines including glial tumor cells with the array, and obtained successful results.3) We analyzed 8 cases of spinal ependymoma and 8 cases of intracranial ependymoma with the DNA array, and identified several characteristic genes for spinal ependymoma (H-ras, M-ras, NCAM, ICAM-2, PDGFR-alpha, FGFR-3, p19INK4d) and intracranial ependymoma (VEGF, p57Kip2, MIP3alpha, MDM2, cyclin D3, TGFbeta2).4) We found that spinal and intracranial ependymomas were well discriminated by pattern classification algorithms including cluster analysis and support vector machine with these expression profiles.5) With more detailed analysis, we found that the two entities of ependymomas were best classified with STAT1 and MIP-3alpha using of a support vector machine. We are now analysing biological significance of these molecules in ependymomas.