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

颅内室管膜瘤与颅内室管膜瘤生物恶性差异的分子病理学分析

• 批准号: 12671338
• 负责人: IWASAKI Yoshinobu
• 金额: $ 2.18万
• 依托单位: HOKAKIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671338/
• 关键词: ependymoma; astrocytoma; spinal cord; brain; DNA array analysis; molecular biology; aslrocytoma

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.

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。

项目成果

Kataoka A, et al.: "Development of a yeast stop codon assay readily and generaly applicable to human genes"Am J Pathol. 159. 1239-1245 (2001)

Kataoka A 等人：“开发一种容易且普遍适用于人类基因的酵母终止密码子测定法”Am J Pathol。

Tada M, et al.: "Inactivate the remaining p53 allele or the altemate p73?-Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants"Carcinogenesis. 22. 1239-1245 (2001)

Tada M 等人：“使剩余的 p53 等位基因或替代的 p73 失活？-在具有隐性 p53 突变体但不具有跨显性突变体的癌症中优先选择 Arg72 多态性”致癌作用。

Uramoto H, Tada M, et al.: "p73 interacts with c-Myc to regulate YB-1 expression"J Biol Chem. 277. 31694-31702 (2002)

Uramoto H、Tada M 等人：“p73 与 c-Myc 相互作用以调节 YB-1 表达”J Biol Chem。

多田光宏: "脳神経外科医に必要な分子生物学"三輪書店,東京(分担). 86-99 (2001)

Mitsuhiro Tada：“神经外科医生必需的分子生物学”Miwa Shoten，东京（合著者）86-99（2001）。

Hida K, et al.: "MRI at 1.5 T of intramedullary ependymoma and classification of pattern of contrast enhancement"Neuroradiology. 42. 828-832 (2000)

Hida K 等人：“髓内室管膜瘤的 1.5 T MRI 和对比增强模式的分类”神经放射学。