Molecular Etiology of Glioblastomas: Implication of Genomic Profiling From the Cancer Genome Atlas Project

Abstract

GlioblastomaGlioblastoma is the most common form of primary brain tumor, with dismal prognosis. The incidence of this tumor is fairly low, with 2-3 cases per 100,000 people in Europe and North America. Despite its rarity, overall mortality related to glioblastoma is comparable to the more prevalent tumors 5 . This is, in large part, due to the near uniform fatality of the afflicted patients. Indeed, glioblastoma is one of the most aggressive of the malignant tumors. Without treatment, the median survival is approximately 3 months 6 . The current standard of treatment involves maximal surgical resection followed by concurrent radiation therapy and www.intechopen.com Glioma -Exploring Its Biology and Practical Relevance 26 chemotherapy with the DNA alkylating agent, temozolomide 7 . With this regimen, the median survival is approximately 14 months. For nearly all affected, the treatments available remain palliative. Studies carried out over the past three decades suggest that glioblastomas, like other cancers, arise secondary to the accumulation of genetic alterations. These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications, or deletions, and modify gene function in ways that deregulate cellular signaling pathways leading to the cancer phenotype 1 . The exact number and nature of genetic alterations and deregulated signaling pathways required for tumorogenesis remains an issue of debate 8 , although it is now clear that CNS carcinogenesis requires multiple disruptions to the normal cellular circuitry 3, 4 .