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

本项目旨在揭示脊髓室管膜瘤与颅内室管膜瘤的分子病理学差异，这两种肿瘤表现为不同的生物学恶性肿瘤。1)我们开发了一种基于酵母的终止密码子检测方法来检测截断型突变，以分析室管膜瘤的分子病理学(Am。j .分册)。2)开发了包含1300个基因的原始DNA阵列。我们用该阵列分析了包括胶质肿瘤细胞在内的119种癌细胞，并获得了成功的结果。3)对8例脊髓室管膜瘤和8例颅内室管膜瘤进行DNA阵列分析，鉴定出脊髓室管膜瘤的几个特征基因（H-ras、M-ras、NCAM、ICAM-2、pdgfr - α、FGFR-3、p19INK4d）和颅内室管膜瘤的几个特征基因（VEGF、p57Kip2、mip3 α、MDM2、cyclin D3、TGFbeta2）。4)我们发现，基于这些表达谱的聚类分析和支持向量机等模式分类算法能够很好地区分脊髓和颅内室管膜瘤。5)通过更详细的分析，我们发现使用支持向量机对两种室管膜瘤进行STAT1和MIP-3alpha分类是最好的。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.