Abstract
It is generally accepted that the accumulation of multiple genetic alterations is essential for development of human tumor. The altered genes can be classified into 5 groups according to their function : (1) cell growth factor and its receptor genes, (2) cell cycle regulator genes, (3) DNA repair genes, (4) genes related to cell invasion and adhesion, (5) genes for angiogenesis. We speculate that at least one out of each group of genes is required for the development of glial tumors. Two different kinds of glioblastomas are proposed, that is, the progression type and the de novo type. The former is believed to be associated with p53 alteration, but the latter is not. The p53 alteration can cause the cell cycle disregulation, failure of DNA repair, impairment of apoptosis induction, acceleration of neovascularization and acquisition of drug resistance. Unexpectedly, the de novo type glioblastomas, which are with wild type p53, show worse clinical course than the progression type glioblastomas. Regarding the de novo type glioblastomas, certain alternative genetic changes other than p53 alteration may act as more adverse factor(s). Recently, it has been shown that the genetic alterations on chromosome 10, such as FGFR2, Mxi-1, PTEN and DMBT1, are frequently seen in glioblastomas. The authors verified that the alteration of FGFR2 was closely associated with unfavorable clinical outcome of the patients with glioblastoma. Thus, genotypic analysis of brain tumors will provide the essential information for selecting the modality of treatment as well as predicting the prognosis.
