Genetic Alterations of Glioblastoma

Abstract

The current research in oncology is focused on genetics and molecular oncology in order to obtain better understanding of the etiology of tumor disease. Detailed knowledge of oncogenesis mechanisms could lead to invention of effective therapeutic tools against cancer. Under healthy conditions, cell cycle is regulated by oncogenes and tumor suppressor genes, which should be in strict balance. Genesis of tumor is a consequence of the accumulation of genetic alterations, which help the cell to escape normal cellular regulatory mechanisms and destruction by immune system. Glioblastoma GBM is a highly malignant primary brain tumor occurring mostly in population of adults. Patients suffering from GBM have very poor prognosis. Despite development in radiology methods promising earlier diagnosis and development of clinical and radiation oncology with newer treatment regimes, the effect of therapy remains limited and prognosis of patients has not improved as expected. Target of GBM research are genes involved in response to oxidative stress and DNA damage, genes regulating cell cycle, genes determining immune response, growth factors, and others. Genetic alterations are studied in connection to their possible relationship to susceptibility of brain tissue for tumor formation, to sensitivity of brain tissue for various environmental etiology factors, to effect of anticancer treatment or resistance of tumor tissue to therapy, to overall survival, and progression-free interval.Keywords: glioblastoma, genes, alteration, mutations, genetic pathways . IntroductionGlioblastoma 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 [ ]. 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 IV according to the WHO classification of brain tumors from . This lesion has a rapid growth, 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 for...