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In WHO grade II astrocytomas, autocrine stimulation by the platelet\u2010derived growth factor system coupled with inactiva\u2010tion of the <jats:italic>p53<\/jats:italic> gene may lead to a growth stimulus in the face of decreased cell death with slow net growth ensuing. Such cells would also have defective responses to DNA damage and impaired DNA repair, setting the stage for future malignant change. Such biological scenarios recapitulate many of the clinicopathological features of WHO grade II astrocytomas. Anaplastic astrocytomas further display release of a critical cell cycle brake that involves the <jats:italic>CDKN2\/p16, RB<\/jats:italic> and <jats:italic>CDK4<\/jats:italic> genes. This results in mitoses seen histologically; clinically, there is more conspicuous, rapid growth. Finally, glioblastomas may emerge from the microenviron\u2010mental outgrowth of more malignant clones in a complex vicious cycle that involves necrosis, hypoxia, growth factor release, angiogenesis and clonal selection; growth signals mediated by activation of epidermal growth factor receptors may precipitate glioblastomas. It is clear as well that glioblastoma multiforme can arise via a number of independent genetic pathways, although the clinical significance of these distinctions remains unclear.<\/jats:p>","DOI":"10.1111\/j.1750-3639.1997.tb01062.x","type":"journal-article","created":{"date-parts":[[2008,1,29]],"date-time":"2008-01-29T05:43:50Z","timestamp":1201585430000},"page":"755-764","source":"Crossref","is-referenced-by-count":141,"title":["A Molecular Genetic Model of Astrocytoma Histopathology"],"prefix":"10.1111","volume":"7","author":[{"given":"David N.","family":"Louis","sequence":"first","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2008,1,28]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"999","article-title":"Human gliomas with wild\u2010type p53 express bcl\u20102","volume":"55","author":"Alderson LM","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_1_3_2","first-page":"2746","article-title":"Loss of wild\u2010type p53 bestows a growth advantage on 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