**1. Introduction**

Glioblastoma (GBM) is a brain tumor of neuroectodermal origin. It is a second most common primary brain neoplasm and the most common from malignant brain tumors. This tumor arises from neural stem cells (NSCs), progenitor cells, dedifferentiated mature neural cells or neuroepithelial stem cells that transform into cancer stem cells (CSCs) or glioblastoma stem (GSC) or stem-like cells [1]. Stem cells have a high potential of self-renewal and differentia‐

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

tion. GBM is a tumor with highest degree of anaplasia within gliomas. It is classified as grade IVaccordingtotheWHOclassificationofbraintumors from2007.This lesionhasarapidgrowth, is unbounded, infiltrates surrounding brain tissue, but rarely metastasizes. When metastases occur, it is usually within the central nervous system. Typical histopathological features of this tumor are cells of recognizably astrocyte origin, but displaying cellular pleomorphism with multinucleation, frequent mitoses, and areas of necrosis surrounded by palisading nuclei (increased tumor cell density) and endothelial proliferation as a manifestation of cellular hyperplasia with numerous clusters of blood vessels forming so-called glomeruloid forma‐ tions. GBM cells spread along tracts in white matter infiltrate cerebrospinal fluid and vessels between meningeal layers. Invasion of GBM cells begins with the degradation of surrounding matrix proteins by proteases and proteinases. Movement of tumor cells through surrounding brain tissue requires receptor turnover, formation and degradation of focal adhesion mole‐ culesandrearrangementofcytoskeletoncomponents.Thesechangesareconsequencesofgenetic alterations, suchas overexpression, amplification,deletionormutationinfocal adhesionkinase and phosphatidylinositol 3-kinase (PI3K) pathways [2] and mainly caused by activation of growth factors and their receptors (integrins and protein deleted in colorectal cancer (DCC), hyaluronreceptorsCD44,RHAMM,BEHAB,ontogeneticproteinSPARC,receptorsforplateletderived growth factor (PDGF), transforming growth factor (TGF)-α, epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF)). Some components of extracellular matrix such as laminin or fibronectin are overexpressed in GBM and their silencing reduces invasive‐ nessofGBMcells [3].Besidesmicroscopic characteristics,GBMis connectedwithahugeamount of genetic alterations causing higher proliferation, migration, and invasiveness of tumor cells. The intrinsic ability of GBM cells to invade normal brain tissue impedes complete surgical resection and predictably results in early local recurrence and mortality. Thoroughgoing explanation of GBM genetic pathways with their gene alterations is necessary for choosing of more suitable therapy and in predicting patient prognosis. This chapter offers an overview of the most common genetic alterations occurring in GBM.
