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Analysis of glioblastoma stem cell derived from bone marrow stem cell using high-resolution array-based comparative genomic hybridization

使用基于高分辨率阵列的比较基因组杂交分析源自骨髓干细胞的胶质母细胞瘤干细胞

基本信息

批准号：
17390403
负责人：
MINETA Toshihiro
金额：
$ 9.92万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390403/
关键词：
brain tumor glioblastoma genomic analysis cancer stem cell array-CGH array-CGH

项目摘要

Dpite great efforts in basic life science and clinical esearch, little progress has been made in mproving the prognosis for patients with glioblastomas. urgical cure of gliomas is impossible in practice because of their high infiltrating activity. The clinical course is dependent upon the biological behavior of the tumor cells. There is increasing evidence that the accumulation of genetic and epigenetic alterations is essential for tumor initiation and progression. Conventional comparative genomic hybridization(metaphase-CGH)_4 has been widely used to screen for chromosomal gains and losses throughout the entiregenome of a tumor. Microarraybased CGH (array-CGH) is a recently developed genomicanalysis technology that enables high-throughputscreening of gene aberrations with sensitivity to detect single gene copy changes. In this study, we employed array CGH formapping of copy number alterations in glioblastomas and analyzed the potential correlation between genomic changes and prognosis … More of patients. We examined whole genomic aberrations of biopsied samples from glioblastomas by array-based comparative genomic hybridization analysis. The highest frequencies of copy number gains were observed on RFC2 (73.3%), EGFR (63.2%), and FGR, ELN, CDKN1C, FES, TOP2A, and ARSA (57.9% each). The highest frequencies of copy number losses were detected on TBR1(52.6%), BMI1 (52.6%), EGR2 (47.4%), DMBT1 (47.4%), MTAP (42.1%), and FGFR2 (42.1%). The copy numbergains of CDKN1C and INS and the copy number losses of TBR1 were significantly correlated with longer survival of patients. High-level amplifications were identified on EGFR, SAS/CDK4, PDGFRA, MDM2, and ARSA. These genes are assumed to be involved in tumorigenesis or progression of glioblastomas. The present study indicates that array-based comparative genomic hybridization analysis has great potential for assessment of copy number changes and altered chromosomal regions of brain tumors. Furthermore, we show that nonlinear analysis methods of whole genome copy number profiles may provide prognostic information about glioblastoma patients. Less

尽管在基础生命科学和临床研究方面做出了很大努力，但在改善胶质母细胞瘤患者预后方面进展甚微。由于胶质瘤的高度浸润性，手术治疗在实践中是不可能的。临床病程取决于肿瘤细胞的生物学行为。越来越多的证据表明，遗传和表观遗传改变的积累对肿瘤的发生和发展是必不可少的。传统的比较基因组杂交(MEDASE-CGH)_4已被广泛用于筛选整个肿瘤基因组中的染色体得失。基于微阵列的CGH(ARRAY-CGH)是最近发展起来的一种基因组分析技术，它能够对基因异常进行高通量筛查，并灵敏地检测单个基因拷贝的变化。在这项研究中，我们使用阵列计算全息成像技术研究了胶质母细胞瘤中拷贝数的改变，并分析了基因组改变与预后…之间的潜在相关性。更多的病人。我们通过基于阵列的比较基因组杂交分析检测了来自胶质母细胞瘤的活检样本的全基因组畸变率。拷贝数增加频率最高的是RFC2(73.3%)、EGFR(63.2%)、FGR、ELN、CDKN1C、FES、TOP2A和ARSA(分别为57.9%)。拷贝数丢失频率最高的是TBR1(52.6%)、BMI1(52.6%)、EGR2(47.4%)、DMBT1(47.4%)、MTAP(42.1%)和FGFR2(42.1%)。CDKN1C和INS基因拷贝数增加和TBR1基因拷贝数丢失与患者的较长生存期显著相关。在EGFR、SAS/CDK4、PDGFRA、MDM2和ARSA上发现了高水平的扩增。这些基因被认为与胶质母细胞瘤的发生或发展有关。本研究表明，基于阵列的比较基因组杂交分析在评估脑肿瘤的拷贝数变化和染色体区域改变方面具有很大的潜力。此外，我们还表明，全基因组拷贝数谱的非线性分析方法可以提供胶质母细胞瘤患者的预后信息。较少