Molecular pathogenesis of malignant gliomas.
De novo glioblastomas develop in older patients without prior clinical history of less malignant tumors. Progressive glioblastomas are common among younger patients and arise through progression from lower-grade astrocytomas. CDKN2A deletions, PTEN alterations, and EGFR amplification are more prevalent among de novo glioblastomas, whereas p53 mutations are more common among progressive glioblastomas. Loss of heterozygosity (LOH) for chromosome 10 is seen uniformly among both de novo and progressive high-grade astrocytomas. The inactivation of the PTEN gene is found in approximately 30% to 40% of astrocytomas with chromosome 10 loss, and LOH pattern in the remaining astrocytomas strongly supports the presence of another yet unidentified tumor suppressor gene telomeric to PTEN. More than 80% of oligodendrogliomas exhibit LOH for 1 p and 19q alleles. Oligoastrocytomas with 1p/19q LOH are related to oligodendrogliomas, and those with p53 mutations are related to astrocytomas.
D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005784:Gene Amplification; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D025521:Tumor Suppressor Proteins