Abstract
Glioblastomas may develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytomas, (secondary glioblastomas). These subtypes of glioblastoma constitute distinct disease entities that evolve through different genetic pathways, affect patients at different ages, and are likely to differ in prognosis and response to therapy. Primary glioblastomas develop in older patients and typically show EGFR overexpression, PTEN (MMAC1) mutations, CDKN2A (p16) deletions, and less frequently, MDM2 amplification. Secondary glioblastomas develop in younger patients and often contain TP53 mutations as the earliest detectable alteration. These characteristics are derived largely from patients selected on the basis of clinical history and sequential biopsies. Currently available data are insufficient for a substitution of histologic classification and grading of astrocytic tumors by genetic typing alone. More subtypes of glioblastomas may exist with intermediate clinical and genetic profiles, a factor exemplified by the giant-cell glioblastoma that clinically and genetically occupies a hybrid position between primary (de novo) and secondary glioblastomas. Future research should aim at the identification of criteria for a combined clinical, histologic, and genetic classification of astrocytic tumors.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adult
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Age Distribution
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Brain Neoplasms / classification
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Brain Neoplasms / diagnosis
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Brain Neoplasms / genetics
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Brain Neoplasms / pathology*
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Cell Transformation, Neoplastic / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / physiology
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Disease Progression
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ErbB Receptors / genetics
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ErbB Receptors / physiology
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Female
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Gene Expression Regulation, Neoplastic
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Genes, DCC
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Genes, Retinoblastoma
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Genes, p16
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Genes, p53
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Genotype
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Glioblastoma / classification
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Glioblastoma / diagnosis
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Glioblastoma / genetics
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Glioblastoma / pathology*
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Humans
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Loss of Heterozygosity
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Macromolecular Substances
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Male
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Middle Aged
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Nuclear Proteins*
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Phenotype
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-mdm2
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Receptors, Platelet-Derived Growth Factor / genetics
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Receptors, Platelet-Derived Growth Factor / physiology
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Retinoblastoma Protein / physiology
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Sex Distribution
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Terminology as Topic
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Tumor Suppressor Protein p53 / physiology
Substances
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Cyclin-Dependent Kinase Inhibitor p16
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Macromolecular Substances
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Neoplasm Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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Retinoblastoma Protein
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2
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ErbB Receptors
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Receptors, Platelet-Derived Growth Factor