Pathways of oncogenesis in primary brain tumors.
Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Steck
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PA
University of Texas M.D. Anderson Cancer Center, Houston.
Saya
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H
D001932:Brain Neoplasms / Q000209:etiology*; D002869:Chromosome Aberrations; D015870:Gene Expression; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D009456:Neurofibromatosis 1 / Q000235:genetics; D009857:Oncogenes