Zhuo, N. | Search bioRxiv

bioRxiv2022

The First Insight into the Epigenetic Fusion Gene Landscape of Acute Myeloid Leukemia

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.

genomics↗

bioRxiv2022

The Hereditary and Epigenetic Fusion Gene Signatures of Multiple Myeloma

Fusion transcripts are thought to be somatic and associated with cancer. However, they have been observed in healthy tissues at high recurrent frequencies. We have used SCIF (SplicingCodes Identify Fusion Transcripts) to analyze RNA-Seq data from 727 multiple myeloma (MM) patients of the MMRF CoMMpass Study. MTG1-SCART1, SCART1-CYP2E1, and TPM4-KLF2 have been detected in 96.1%, 95.7%, and 92.2% of 727 MM patients and formed fusion gene signatures. MTG1-SCART1 and SCART1-CYP2E1 are read-through from the same locus and the two most recurrent epigenetic fusion genes (EFGs) out of 187 EFGs detected in [≥]10% of 727 MM patients. TPM4-KLF2 fusion gene, which was initially thought to be somatic, has been shown by a monozygotic twin genetic model to be a hereditary fusion gene (HFG) and the dominant genetic factor associated with MM. This work provides the first line of evidence that HFGs are the genetic factors and EFGs reflect the consequences between genetics and environments during development.

cancer biology↗