RT Journal Article
SR Electronic
T1 The Hereditary and Epigenetic Fusion Gene Signatures of Multiple Myeloma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.05.519213
DO 10.1101/2022.12.05.519213
A1 Fei, Ling
A1 Zhuo, Noah
A1 Zhuo, Degen
YR 2022
UL http://biorxiv.org/content/early/2022/12/08/2022.12.05.519213.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.