Other environmental exposures to vinyl chloride, pesticides, smoking, petroleum refining, and synthetic rubber manufacturing have been loosely associated with the development of gliomas. Radiation-induced GBM is typically seen years after therapeutic radiation indicated for another tumor or condition ( Johnson et al., 2015). Ionizing radiation is one of the few known risk factors to definitely show an increased risk of glioma development ( Ellor et al., 2014). Molecular subtyping shows promise in identifying subsets that may be uniquely responsive to specific adjuvant therapies ( Vitucci, Hayes, & Miller, 2011), and future therapies will likely be tailored to target these underlying molecular abnormalities.Įfforts to identify specific associations of this disease with environmental and occupational exposure have largely been inconclusive and underpowered.
Imaging genomics is an emerging science that explores associations between molecular profiles and radiologic features and may eventually serve as a noninvasive technique to determine genomic correlation, prediction, and identification ( Moton, Elbanan, Zinn, & Colen, 2015). Methods to determine a patient’s tumor subtype require an invasive biopsy or surgical resection to perform genomic analysis. For a more detailed analysis of GBM signaling pathways and subtypes, readers are referred to Brennan et al., 2013 Verhaak et al., 2010 and Wang et al., 2015.
In addition, four GBM subtypes have been identified (i.e., classical, pro-neural, neural, and mesenchymal), each with distinctly different patterns of disease progression and survival outcomes. In secondary GBM, isocitrate dehydrogenase 1 (IDH1) mutations, p53 mutations, and chromosome 19q loss are frequently seen ( Alifieris & Trafalis, 2015 Wilson et al., 2014 Young, Jamshidi, Davis, & Sherman, 2015). Genetic alterations typical for primary GBM are epidermal growth factor receptor (EGFR) overexpression, phosphate and tensin homologue (PTEN) mutations, and loss of chromosome 10q. Molecular alterations or gene expression patterns have also been recognized between primary and secondary gliomas. The majority of primary and secondary GBMs have alterations in these pathways, giving rise to uncontrolled cell proliferation and enhanced cell survival, while also allowing the tumor cell to escape from cell-cycle checkpoints, senescence, and apoptosis pathways ( Chen, McKay, & Parada, 2012). A majority of GBMs are primary, and these patients tend to be older aged and have a poorer prognosis than patients with secondary GBMs ( Wilson, Karajannis, & Harter, 2014).Īs a result of genomic profiling and the Cancer Genome Atlas project ( Parsons et al., 2008), more than 600 genes were sequenced from greater than 200 human tumor samples, which revealed the complicated genetic profile of GBM and established a set of three core signaling pathways that are commonly activated (i.e., the tumor protein p53 pathway, the receptor tyrosine kinase/Ras/phosphoinositide 3-kinase signaling pathway, and the retinoblastoma pathway). GBMs can be classified as primary, or de novo, arising without a known precursor or secondary, where a low-grade tumor transforms over time into GBM. Incidence is slightly higher in men than women (1.6:1) and in Caucasians relative to other ethnicities ( Ellor, Pagano-Young, & Avgeropoulos, 2014). GBMs present at a median age of 64 years ( Thakkar et al., 2014) but can occur at any age, including childhood. These cells are at multiple stages of differentiation from stem cell to neuron to glia, with phenotypic variations determined, in large part, by molecular alterations in signaling pathways rather than by differences in cell type of origin ( Phillips et al., 2006). Originally, GBMs were thought to be derived solely from glial cells however, evidence suggests that they may arise from multiple cell types with neural stem cell–like properties. Sixty-one percent of all primary gliomas occur in the four lobes of the brain: frontal (25%), temporal (20%), parietal (13%), and occipital (3%) ( American Association of Neuroscience Nurses, 2014). Although GBMs occur almost exclusively in the brain, they can also appear in the brain stem, cerebellum, and spinal cord. The average age-adjusted incidence rate is 3.2 per 100,000 population ( Ostrom et al., 2015 Ostrom, Gittleman, et al., 2014). Glioblastoma (GBM) is the most common primary malignant brain tumor, comprising 16% of all primary brain and central nervous system neoplasms ( Thakkar et al., 2014).
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