Validation and Characterization of Novel FCHSD2 Translocations Identified in Multiple Myeloma
Multiple myeloma is a genetically heterogeneous disease, which can be divided into several genetic subtypes based upon gene expression profiles and chromosomal abnormalities. Unlike older techniques employed in myeloma research, such as cytogenetics, FISH, and microarray technologies, RNA sequencing offers a unique approach to examine the aforementioned genetic characteristics in that it allows for gene expression profiling and the detection of novel fusion transcripts arising from chromosomal rearrangements. This study utilized RNA sequencing to analyze the transcriptomes of 84 multiple myeloma patients and 69 human myeloma cell lines. FCHSD2 was found to be involved in five novel fusion events along with known oncogenes, MMSET and MYC, as well as three previously unreported genes in myeloma, including CHMP4B, NCF2, and CARNS1. An analysis of FCHSD2 expression within myeloma cell lines indicated that it is highly expressed in comparison to other tissues, suggesting that FCHSD2 translocations could lead to promoter replacement events in which the expression of partnering genes is dysregulated. The presence of the five FCHSD2 hybrid transcripts was confirmed by reverse transcription-PCR and Sanger sequencing. Overexpression of the FCHSD2 fusion transcripts in HEK293 cells resulted in the production of N-terminally truncated fusion partner proteins and a novel FCHSD2-CARNS1 fusion protein.
- Murray, Christopher William (Author)
- Wilson-Rawls, Jeanne (Thesis director)
- Carpten, John (Committee member)
- Keats, Jonathan (Committee member)
- Barrett, The Honors College (Contributor)
- School of Life Sciences (Contributor)