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Molecular diagnosis of glioblastomas based on genetic alterations.

基于遗传改变的胶质母细胞瘤的分子诊断。

基本信息

批准号：
09470298
负责人：
TABUCHI Kazuo
金额：
$ 8.64万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470298/
关键词：
glioma p53 p16 FGFR2 Mxi-1 prognosis PTEN chromosome 10 Mxi-1 Chromosome 10

项目摘要

(1) Gene alteration and clinical outcome of gliomasWe focused on the alteration of the genes on chromosome 10, such as Ret, PTEN, Mxi, FGFR2, DMBT1, as well as the commonest alterations of p53 and p16 genes. We have analysed the relationship of the alteratio of these genes and the clinical course of each cases. As the result, the worst factors affecting the survival period of glioblastomas were habouring wild-type p53 gene and the loss of FGFR2 gene. It have been reported that the PTEN altered glioblastoma present worse clinical course, however we could not detect any differences of survival period between PTEN altered and wild glioblastoma. The PTEN gene alterations were detected equal incidence in p53 wild and p53 altered glioblastoma. Thus we considered that the p53 alteration and PTEN alteration are independent prognostic factors in glioblastomas.(2) Detection of SV4O genome in glioblastomas.Among the glioblastomas of high-aged patient we detected a part of SV4O sequences by PCR, as well as in situ hybridization. We could not detected the expression of T antigen in any of these patients. It could be possible that there is a certain inactivating mechanisms for T antigen, or unknown survival mechanisms for SV4O without T antigen in glioblastoma. These fact strongly suggest that the viral infection implicated in glial tumorigenesis.According to the molecular background of the glioblastomas, a noble classification is going to be established. The molecular diagnosis of glioblastomas based on genetic alteration could reflect the biological feature of glioblastomas.

(1)胶质瘤的基因改变与临床结局我们重点研究了10号染色体上Ret、PTEN、Mxi、FGFR2、DMBT1等基因的改变，以及最常见的p53、p16基因的改变。我们分析了这些基因的改变与每个病例的临床病程的关系。因此，影响胶质母细胞瘤生存期的最坏因素是携带野生型p53基因和FGFR2基因的缺失。据报道，PTEN改变的胶质母细胞瘤的临床病程较差，但我们未发现PTEN改变的胶质母细胞瘤与野生胶质母细胞瘤的生存期有任何差异。PTEN基因改变在p53野生型和p53改变型胶质母细胞瘤中的发生率相等。因此，我们认为p53改变和PTEN改变是胶质母细胞瘤的独立预后因素。(2)胶质母细胞瘤sv40o基因组的检测。在高龄患者的胶质母细胞瘤中，我们通过PCR和原位杂交检测到部分sv40o序列。我们在这些患者中均未检测到T抗原的表达。在胶质母细胞瘤中，可能存在T抗原灭活机制，或者没有T抗原的sv40o存在未知的存活机制。这些事实强烈提示病毒感染与神经胶质瘤的发生有关。根据胶质母细胞瘤的分子背景，将建立一个高贵的分类。基于基因改变的胶质母细胞瘤分子诊断能够反映胶质母细胞瘤的生物学特征。