Molecular diagnosis of glioblastomas based on genetic alterations.

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(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.