Phenotype vs genotype in the evolution of astrocytic brain tumors

Astrocytic brain tumors are the most frequent human gliomas and they includ e a wide range of neoplasms with distinct clinical, histopathologic, and ge neric features. Diffuse astrocytomas are predominantly located in the cereb ral hemispheres of adults and have an inherent tendency to progress to anap lastic astrocytoma and (secondary) glioblastoma. The majority of glioblasto mas develop de novo (primary glioblastomas), without an identifiable less-m alignant precursor lesion. These subtypes of glioblastoma evolve through di fferent genetic pathways, affect patients at different ages, and are likely to differ in their responses to therapy. primary glioblastomas occur in ol der patients and typically show epidermal growth factor receptor (EGFR) ove rexpression, PTEN mutations, p16 deletions, and, less frequently, MDM2 ampl ification. Secondary glioblastomas develop in younger patients and often co ntain TP53 mutations as their earliest detectable alteration. Morphologic v ariants of glioblastoma were shown to have intermediate clinical and geneti c profiles. The giant cell glioblastoma clinically and genetically occupies a hybrid position between primary (de novo) and secondary glioblastomas. G liosarcomas show identical gene mutations in the gliomatous and sarcomatous tumor components, which strongly supports the concept that there is a mono clonal origin for gliosarcomas and an evolution of the sarcomatous componen t due to aberrant mesenchymal differentiation in a highly malignant astrocy tic neoplasm.