Abstract
Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.
Highlights
Brain tumors are highly heterogeneous and the currently most used classification of these tumors is that proposed by the World Health Organization (WHO) (Table 1)
The comparison of somatic alterations in adult and pediatric glioblastomas showed some remarkable differences: EGFR, TERTp, and PTEN mutations were more frequent in adult than in pediatric glioblastomas; H3FA, HIST 3.1 B/C, ATRX, SETD2, and BRAFV600E mutations are more frequent in pediatric than in adult glioblastomas; EGFR and CDK4 amplifications are more frequent in adult than pediatric glioblastoma; focal or intragenic deletions of EGFR or CDKN2A are more frequent in adult than pediatric glioblastomas; some chromosome gains, such as chromosomes 1, 19, and 20 are more frequent in adult than pediatric glioblastomas, while the contrary was observed for 1q gain; chromosome 10, 9p, and 6q loss was more frequent in adult than in pediatric glioblastomas [56] (Figure 1B)
This analysis demonstrated that (a) different glioblastoma subtypes are present within the same tumor; (b) the analysis of the intratumor heterogeneity of these tumors allowed a reconstruction of the phylogeny of the tumor fragments for each patient, identifying copy number alterations in EGFR and CDKN2A/B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progression; and (c) the analysis of individual tumor cells showed the coexistence of multiple genetic abnormalities [37]
Summary
Brain tumors are highly heterogeneous and the currently most used classification of these tumors is that proposed by the World Health Organization (WHO) (Table 1). WHO grade I pilocytic astrocytomas correspond to 5–6% of all gliomas, occur in children/young patients, and are composed of compact bundles of piloid/elongated cells containing nuclei with minimal atypia (the majority of these tumors are curable by tumor excision) In contrast to these localized astrocytomas, the majority of astrocytomas are diffuse astrocytomas, developing in the cerebral hemispheres and exhibiting a great capacity to infiltrate the surrounding brain parenchyma. Sci. 2018, 6, 85 the cerebral hemispheres: these tumors are characterized by a high proliferation index (17% ± 10%), marked cellular heterogeneity, pronounced nuclear atypia, and the capacity to highly infiltrate adjacent normal brain tissue In addition to these properties, glioblastomas are characterized by a marked endothelial cell proliferation, forming multilayered vessels and areas of necrosis. Medulloepithelioma Embryonal tumor with multilayered rosettes, C19M altered CNS embryonal tumor
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