Molecular diagnosis of glioblastomas based on genetic alterations.

(1)胶质瘤的基因改变及临床转归我们重点研究了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差因素是野生型P53基因和FGFR2基因缺失。据报道，PTEN基因改变的胶质母细胞瘤的临床病程较差，但我们没有发现PTEN基因改变的胶质母细胞瘤与野生型胶质母细胞瘤的生存期有任何差异。在P53野生型和P53变异型胶质母细胞瘤中，PTEN基因改变的发生率相同。因此，我们认为P53和PTEN的改变是胶质母细胞瘤中独立的预后因素。(2)胶质母细胞瘤中SV4O基因组的检测。所有患者均未检测到T抗原的表达。在胶质母细胞瘤中，可能存在一定的T抗原失活机制，也可能存在未知的SV4O存活机制。这些事实强烈表明病毒感染与胶质细胞肿瘤的发生有关。根据胶质母细胞瘤的分子背景，一个高尚的分类将被建立。基于基因改变的胶质母细胞瘤分子诊断能反映胶质母细胞瘤的生物学特性。

(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.