Discovery of a novel fusion gene in glioblastoma using computational methods

Abstract

Cancer is a disease characterized by the uncontrolled and invasive growth of cells. All forms of cancer are caused by genomic alterations that alter normal cellular function, leading to a malignant phenotype that is inherited across cell division. Fusion genes are a type of genomic alteration where pieces from two genes are fused together, forming a new gene with altered behaviour. Fusion genes are known to play a role in many human cancers. In this work, we used computational analysis and whole transcriptome sequencing to search for fusion genes in a cohort of 40 brain cancer patients. We discovered a novel fusion gene FGFR3-TACC3 that characterizes a new subtype of glioblastoma, a highly lethal form of brain cancer. In a larger validation cohort, the fusion gene was found in 4 of 48 glioblastoma patients but not in any of 43 low-grade gliomas tested. The fusion gene is caused by tandem duplication and encodes a chimeric protein that promotes glioma progression and cell growth. The fusion gene was mutually exclusive with the amplification of EGFR, PDGFRA and MET, three oncogenes associated with glioblastoma. The availability of small molecule inhibitors for FGFR3 suggests an effective treatment strategy for glioblastoma patients harboring the fusion.