Molecular Hallmarks of Gliomas

Abstract

Tumors of the central nervous system (CNS) encompass a wide variety of entities, which span from benign to highly malignant. The classification of these tumors is typically based on their histopathological features or their location within the CNS. Despite these apparently simple criteria, there are a great number of independent CNS tumor types as defined by the most recent World Health Organization (WHO) classification of CNS tumors (Louis et al., 2007), which is the standard for the definition of CNS tumors worldwide. The WHO listing of CNS tumors is impressively vast and has, in fact, been surrounded by some controversy concerning the nosology of some tumor entities (e.g., the nosologic place of highly anaplastic oligoastrocytic tumors, glioblastoma with oligodendroglioma components). The agestandardized incidence rate of all primary non-malignant and malignant CNS tumors in the US is 16.5 per 100,000 person–years (9.2 per 100,000 person–years for non–malignant tumors and 7.3 per 100,000 person–years for malignant tumors) (CBTRUS, 2010). This rate is higher in females (17.2 per 100,000 person–years) than males (15.8 per 100,000 person–years). Worldwide data is available only for malignant primary CNS tumors; in this setting, the incidence rates are higher in males (approximately 3.7 per 100,000 person-years) than females (2.6 per 100,000 person–years) (Ferlay et al., 2008). In Western Europe, the male and female incidence rates of malignant CNS tumors are 6.7 per 100,000 person-years and 4.5 per 100,000 person-years, respectively. Very similar figures are observed in Northern America (6.0 and 4.5 per 100,000 person-years for males and females, respectively). Interestingly, the incidence rates are higher in more developed countries than in less developed ones, but these differences may be a consequence of differences in diagnostic practices, completeness of reporting and access to adequate health care, rather than attributable to geographic and genetic variation. CNS tumors are considered to be primary when the tumor originally initiates in the CNS, as opposed to the far more common brain metastases derived from malignant tumors located in other organs, which are considered secondary brain tumors. Primary brain and CNS tumors account for only approximately 2% of all primary tumors (Louis et al., 2007), but they rank first among tumor types for the average years of life lost (~20 years, compared, for example, with ~6 years for prostate cancer and ~12 years for lung cancer) (Burnet et al., 2005). These tumors are the most frequent solid malignancy in children, being the leading cause of cancer-related death in children under the age of 19 (Rickert & Paulus, 2001). The impact and nature of primary brain tumors in adults is somewhat different, but they still rank second as cause of cancer death in males aged 20 to 39 years, and fifth in females of