The First Insight into the Epigenetic Fusion Gene Landscape of Acute Myeloid Leukemia
Ling, F.; Zhuo, N.; Zhuo, D.
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Epigenetic fusion genes have been defined as the fusion genes produced via cis-splicing of read-through pre-mRNAs of two identical-strand neighbor genes and have been known for decades. However, they need to be adequately investigated. In this study, we analyze RNA-Seq data from 390 AML patients and identify 12,754 EFG isoforms encoded by 5,213 EFGs, one-sixth of all potential EFGs. We characterize 479 EFG isoforms whose recurrent frequencies range from 10% to 96.2% and show that most of them result from developmental interactions between recurrent inherited genetic and environmental abnormalities. Novel EFG isoforms generated during late developments reflect somatic genetic abnormalities and environmental stresses. These characteristics of EFG isoforms make it possible for clustering heatmap and counting for EFG isoforms to distinguish GTEx healthy individuals and AML patients. This study reveals that human genomes encode potential EFGs equal to the total number of human genes and pseudogenes. EFGs provide one of the most powerful and economical tools to monitor the earliest signals from somatic genetic and environmental abnormalities.
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