Molecular changes involved in the carcinogenesis of brain tumors.
Current basic research on tumorigenesis suggests that the accumulation of multiple genetic defects underlies the progression of initiated cells toward malignancy. Molecular abnormalities associated with primary brain tumors include a wide variety of changes in tumor-suppressor genes, proto-oncogenes and growth factors. A well-known tumor-suppressor gene, p53 gene, is located on the short arm (p) of chromosome 17 and consists of 11 exons transcribed into a 2.2-2.5 kb messenger (m) RNA that encode for a 53 kDa protein. Its alterations are associated with carcinogenesis of astrocytic tumors. Recent evidence suggests also that the p53 protein may function through promoting the expression of the recently discovered gene, WAF1/Cipl. Loss of chromosome 10 was frequently observed in glioblastoma. Southern blot analysis of glioblastomas revealed that 72% have the chromosome 10 loss and that 38% had amplification of the epidermal growth factor receptor (EGFR) gene. Autocrine stimulation of cell growth requires the presence of both growth factors and their receptors. Other genetic alterations in gliomas include elevated expression of the c-myc, Ha-ras, and c-fos oncogenes with a trend to increase in higher malignant grades.
Debiec-Rychter
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Electron Microscopic Laboratory, School of Medicine Lódz.
Liberski
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PP
D001483:Base Sequence; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000473:pathology*; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D066246:ErbB Receptors; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009457:Neuroglia / Q000473:pathology; D010641:Phenotype; D011519:Proto-Oncogenes; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors