Identification of <i>KANSARL</i> as the first cancer predisposition fusion gene specific to the population of European ancestry origin

Abstract

Gene fusion is one of the hallmarks of cancer. Recent advances in RNA-seq of cancer transcriptomes have facilitated the discovery of fusion transcripts. In this study, we report identification of a surprisingly large number of fusion transcripts, including six <i>KANSARL</i> (<i>KANSL1</i>-<i>ARL17A</i>) transcripts that resulted from the fusion between the <i>KANSL1</i> and <i>ARL17A</i> genes using a RNA splicingcode model. Five of these six <i>KANSARL</i> fusion transcripts are novel. By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that <i>KANSARL</i> fusion transcripts were rarely detected in the tumors of individuals from Asia or Africa. In contrast, they exist in 30 - 52% of the tumors from North Americans cancer patients. Analysis of CEPH/Utah Pedigree 1463 has revealed that <i>KANSARL</i> is a familially-inherited fusion gene. Further analysis of RNA-seq datasets of the 1000 Genome Project has indicated that <i>KANSARL</i> fusion gene is specific to 28.9% of the population of European ancestry origin. In summary, we demonstrated that <i>KANSARL</i> is the first cancer predisposition fusion gene associated with genetic backgrounds of European ancestry origin.