Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment. 1. Introduction Gliomas are the most common brain tumor in adults, with very low survival rates, even when combining radio-and chemotherapy. Among the gliomas, glioblastoma multiforme (GBMs) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. GBMs are usually detected upon the incidence of neurological symptoms, rendering it a disease that is diagnosed already at an advanced stage. Other glioma types include astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas, which are characterized according to their histological features. How is it that such a malignancy arises in this carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function? This question has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such doubts. Even so, the precise origin of gliomas still remains elusive. Fortunately, with new advances in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBMs are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic
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