The Hereditary and Epigenetic Fusion Gene Signatures of Multiple Myeloma

Abstract

ABSTRACTFusion 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 (SplicingCodesIdentifyFusion Transcripts) to analyze RNA-Seq data from 727 multiple myeloma (MM) patients of the MMRF CoMMpass Study.MTG1-SCART1, SCART1-CYP2E1, andTPM4-KLF2have been detected in 96.1%, 95.7%, and 92.2% of 727 MM patients and formed fusion gene signatures.MTG1-SCART1andSCART1-CYP2E1are 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-KLF2fusion 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.