Molecular diagnosis of glioblastomas based on genetic alterations.

(1)胶质瘤的基因改变与临床预后我们重点研究了10号染色体上的Ret、PTEN、Mxi、FGFR 2、DMBT 1等基因的改变，以及最常见的p53和p16基因的改变。我们分析了这些基因的改变与每个病例临床病程的关系。结果表明，携带野生型p53基因和FGFR 2基因缺失是影响胶质母细胞瘤生存期的最严重因素。有报道称，PTEN基因突变的胶质母细胞瘤的临床表现较差，但我们没有发现PTEN基因突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。PTEN基因突变在p53野生型和p53突变型胶质母细胞瘤中的发生率相同。因此，我们认为p53和PTEN的改变是胶质母细胞瘤独立的预后因素。(2)胶质母细胞瘤中SV4O基因组的检测：在高年龄胶质母细胞瘤中，我们用PCR和原位杂交方法检测到部分SV4O基因序列。所有患者均未检测到T抗原的表达。可能存在T抗原失活的机制，或无T抗原的SV4O在胶质母细胞瘤中的存活机制尚不清楚。这些事实有力地表明病毒感染参与了胶质瘤的发生，根据胶质母细胞瘤的分子背景，将建立一个高尚的分类。以基因改变为基础的胶质母细胞瘤分子诊断能较好地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.