Microarray Analysis of Gene Expression Profiles in Primary and Secondary Glloblastomas

原发性和继发性成胶质细胞瘤基因表达谱的微阵列分析

• 批准号: 12557114
• 负责人: MORIUCHI Tetsuya
• 金额: $ 8.06万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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/en/grant/KAKENHI-PROJECT-12557114/
• 关键词: glioblastoma; de novo glioblastoma; secondary glioblastoma; PI3K-Akt pathway; p53 functional loss; cDNA array; transcriptome; pattern classification; P13K-Aki pathway; p53 fumcional loss; cDNA aray; Pl3K-Ak1 pathway; PI3K-Akt pathway

Glioblastoma multiforme is classified into two subsets : one is 'primary (de novo) glioblastoma' which arises in relatively elderly persons without a preceding lesion, and another is 'secondary glioblastoma' which arises in young persons with a preceding benign astrocytoma. The present study aimed to analyze mRNA expression profiles of the both subsets, disclose their underlying molecular pathological natures, and know the mechanism which causes the biological and clinical differences between the both subsets.We obtained the following results through this study : 1) We developed a yeast-based stop codon assay to identify PTEN gene mutations that inversely correlate with p53 mutations to classify glioblastomas (Oncogene).2) We developed an original DNA array consisting of 1300 genes. We analyzed 119 cancer cell lines including glioblastoma cells with the array, and obtained successful results.3) We analyzed glioblastoma cell lines including U251MG, SF268, SF295, SF539, SNB-75, and SNB-78, for their p53-, APC- and PTEN-mutational states and their expression profiles. We identified a total of 85 genes that associated with the p53 mutational status.4) We found that application of feature subset selection algorithms and neural networks to extract characteristic patterns of gene expression. We are now undertaking studies on a number of clinical cases of glioblastoma.

多形性胶质母细胞瘤分为两个子集：一个是“原发性（新生）胶质母细胞瘤”，其发生在相对老年人中，没有先前的病变，另一个是“继发性胶质母细胞瘤”，其发生在年轻人中，先前有良性星形细胞瘤。本研究旨在分析两个亚群的mRNA表达谱，揭示其潜在的分子病理学本质，并了解导致两个亚群之间生物学和临床差异的机制。1）我们开发了一种基于酵母的终止密码子分析来鉴定与p53突变负相关的PTEN基因突变，以分类胶质母细胞瘤（Oncogene）。2）我们开发了一个由1300个基因组成的原始DNA阵列。3）分析了U251 MG、SF 268、SF 295、SF 539、SNB-75和SNB-78等胶质母细胞瘤细胞系的p53、APC和PTEN突变状态及其表达谱。我们共鉴定了85个与p53突变状态相关的基因。4）我们发现应用特征子集选择算法和神经网络可以提取基因表达的特征模式。我们现正就多宗胶质母细胞瘤的临床个案进行研究。

项目成果

Ikeda J: "Restoration of endogenous wild type p53 activily in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis"Int J Cancer. 94. 35-43 (2001)

Ikeda J：“在具有内在温度敏感性 p53 的胶质母细胞瘤细胞系中，内源性野生型 p53 的活性恢复会诱导生长停滞，但不会诱导细胞凋亡”Int J Cancer。

Tada M, Furuuchi K, et al.: "Inactivate the Remaining p53 Allele or the Alternate p73? -Preferential selection of the Arg 72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants."Carcinogenesis. (in press). (2001)

Tada M、Furuuchi K 等人：“使剩余 p53 等位基因或替代 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 Arg 72 多态性。”致癌作用。

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. 86-99 (2001)

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

Zhang, C.-L.: "Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay"Oncogene. 19. 4346-4353 (2000)

张，C.-L.：“通过基于酵母的终止密码子测定检测中枢神经系统高级星形细胞肿瘤中的 PTEN 无义突变和 psiPTEN 表达”癌基因。

Tada M: "Inactivate the remaining p53 allele or the alternate p73?-Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants"Carcinogenesis. 22. 515-517 (2001)

Tada M：“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。