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Investigation of Morphological Characteristics and Genetic Aberration in Gliomas Using Microsatellite Markers

利用微卫星标记研究胶质瘤的形态特征和遗传畸变

基本信息

批准号：
07671514
负责人：
MARUNO Motohiko
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

The investigation was performed to establish the correlation between morphological characteristics and the genetic aberration in human gliomas. DNA from gliomas were amplified by polymerase chain reaction to detect loss of heterozygosity (LOH) at 33 microsatellite loci on chromosomes 9,10,17 and 22. The molecular genetic data were compared with immunohistochemistry performed with antibodies to glial fibrillary acidic protein (GFAP), MIB-1 and p53 protein and also with patient survival. Aberration of chromosome 9 was evidenced in 50% of imformative loci in malignant gliomas. Aberration of chromosome 10 was also evidented in 39.7% of the imformative loci in glioblastomas. Moreover, aberrations of chromosome 17 and 22 were rrelatively higher in 9.5%, 20.0% of the imformative loci, respectively, even in benign gliomas. LOH at D22S300 (22q12.1-q13.1) was exclusively seen (80%) in glioblastomas. LOH at 10q22-25 was consistently recognized in glioblastomas after recurrence from astrocytomas or anaplastic astrocytomas suggesting this area is closely relalated with most malignant progression in gliomas. The allelic status of D17S795 (17q21.2) in all informative instances were concordant with GFAP immunoreactivity (P<0.01 ; Fisher's test). Furthermore, the inter-chromosomal relationship disclosed a close correlation between the presence of frequent LOH in chromosome 17 or 22 and the occurrence of LOH in the other 3 chromosomes (R=0.601 ; P<0.01 ; Stepwise regression) suggesting the possible involvement of chromosome 17 and 22 in causing genomic instability. A trend of inverse relationship between the time of recurrence and the presence of LOH on chromosome 10 in anaplastic astrocytoma patients was seen. However, correlation between the presence or absence of LOH and patient survival was not apparent in cases of glioblastomas. The findings underscores the diverse and 'multi-chromosome based' nature of astrocytic tumors.

本研究旨在探讨人脑胶质瘤的形态特征与遗传变异之间的关系。用聚合酶链式反应扩增脑胶质瘤DNA，检测9、10、17和22号染色体上33个微卫星座位的杂合性缺失(LOH)。将分子遗传学数据与抗胶质纤维酸性蛋白(GFAP)、MIB-1和P53蛋白的免疫组织化学方法进行比较，并与患者的生存期进行比较。恶性胶质瘤中有50%的信息位点存在9号染色体的异常。在胶质母细胞瘤中，39.7%的信息位点也存在10号染色体的异常。此外，即使在良性胶质瘤中，17号和22号染色体的畸变率也相对较高，分别为9.5%和20.0%。D22S300(22q12.1-q13.1)杂合性缺失仅见于胶质母细胞瘤(80%)。在星形细胞瘤或间变性星形细胞瘤复发后的胶质母细胞瘤中，10q22-25的LOH一直被发现，这表明该区域与胶质瘤的大多数恶性进展密切相关。D17S795(17q21.2)的等位基因状态与GFAP免疫反应一致(P&lt；0.01；Fisher‘s检验)。此外，染色体间关系显示，17号或22号染色体的频繁杂合性缺失与其他3条染色体的杂合性缺失密切相关(R=0.601；P&lt0.01；逐步回归)，提示17号和22号染色体可能参与了导致基因组不稳定的因素。在间变性星形细胞瘤患者中，复发时间与10号染色体LOH的存在呈负相关趋势。然而，在胶质母细胞瘤病例中，杂合性缺失的存在或不存在与患者生存之间的相关性并不明显。这些发现强调了星形细胞肿瘤的多样性和“基于多染色体”的性质。