Transcription Profiling of Brain Tumors: Tumor Biology and Treatment Stratification

The spectrum and diversity of primary brain tumors has made prognostic determinations based purely on clinicopathologic variables inexact. For the most frequently occurring and lethal tumors, the malignant astrocytomas, the use of large-scale gene expression profiling experiments has led to a better understanding of the biology of these tumors, giving insights into their origin and development, as well as more powerful outcome prediction. It has also paved the way for the possibility of personalized medicine, where a patient’s tumor expression profile can be used to design treatment specific to that individual with the greatest possibility of response. This chapter will focus on the use and development of transcriptional profiles as biomarkers of outcome and treatment response in patients with brain tumors. The discussion will be limited to array-based profiling, as other techniques, such as serial analysis of gene expression (SAGE), have had less widespread use (Ljubimova et al. 2001a; Boon et al. 2003; Boon and Riggins 2003; Beaty et al. 2007; Kavsan et al. 2007). While mRNA-based profiles have been described for a variety of tumors that affect the central nervous system, this chapter will focus particularly on malignant gliomas, to which the majority of large-scale efforts have been focused to date, both due to the larger tumor populations available for analyses and due to the poorer outcome of patients with these devastating tumors (Kleihues et al. 2000; Behin et al. 2003).