Data from Monoallelic Expression Determines Oncogenic Progression and Outcome in Benign and Malignant Brain Tumors

Abstract

<div>Abstract<p>Although monoallelic expression (MAE) is a frequent genomic event in normal tissues, its role in tumorigenesis remains unclear. Here we carried out single-nucleotide polymorphism arrays on DNA and RNA from a large cohort of pediatric and adult brain tumor tissues to determine the genome-wide rate of MAE, its role in specific cancer-related genes, and the clinical consequences of MAE in brain tumors. We also used targeted genotyping to examine the role of tumor-related genes in brain tumor development and specifically examined the clinical consequences of MAE at <i>TP53</i> and <i>IDH1</i>. The genome-wide rate of tumor MAE was higher than in previously described normal tissue and increased with specific tumor grade. Oncogenes, but not tumor suppressors, exhibited significantly higher MAE in high-grade compared with low-grade tumors. This method identified nine novel genes highly associated with MAE. Within cancer-related genes, MAE was gene specific; <i>hTERT</i> was most significantly affected, with a higher frequency of MAE in adult and advanced tumors. Clinically, MAE at <i>TP53</i> exists only in mutated tumors and increases with tumor aggressiveness. MAE toward the normal allele at <i>IDH1</i> conferred worse survival even in <i>IDH1</i> mutated tumors. Taken together, our findings suggest that MAE is tumor and gene specific, frequent in brain tumor subtypes, and may be associated with tumor progression/aggressiveness. Further exploration of MAE at relevant genes may contribute to better understanding of tumor development and determine survival in brain tumor patients. <i>Cancer Res; 72(3); 636–44. ©2011 AACR</i>.</p></div>