The clinical prognosis for brain tumors may vary widely. For example, cerebellar astrocytomas are frequently benign and rarely transform to full malignancy (Conway et al., 1990). Low grade cerebral and brain stem astrocytomas which may be initially characterized as low grade histopathologically, have a greater predisposition to undergo malignant transformation over time (Soffieti et al., 1989). Children under the age of 5 who develop primary primitive neuroectodermal tumors (PNET) of the CNS are more likely to present with widespread CNS metastases with relatively high frequency, while the same family of tumors in children 5-15 years of age is more likely to remain localized (Allen and Epstein, 1982). Furthermore, children in certain genetic high risk groups who are more likely to have underlying molecular genetic alterations such as mutations in tumor suppressor genes (e.g. p53, neurofibromatosis, retinoblastoma). These individuals have an increased probability of brain tumor occurrence (Baptiste et al., 1989). The underlying causes which place certain pediatric or adult populations as outlined above, at high risk for developing CNS neoplasm is not yet known. We propose to examine classes of brain tumors which have different prospects for malignant transformation for evidence of myc family gene deregulation. We will test the hypothesis that in tumors in which Rb and other negative acting functions such as homodimeric Max protein and Myc binding site DNA methylation (Blackwood and Eisenman, 1991; Blackwood et al., in press; Prendergast and Ziff, 1991; Prendergast et al., 1991, Berberich and Cole, in press) are wild type, the myc gene may have to be expressed at high levels to overcome Rb or other recessive oncogene action. this could result through receptor tyrosine kinase gene or myc gene amplification. when Rb or other potential negative regulators are mutant, Myc proteins may be over expressed and able to act without restraint, even without accompanying dominant mutation. Potentially both forms of mutations may occur and both positive and negative acting controls may be lost. We will ask if this is the case for tumors which have transformed to an aggressively malignant state.
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