Functional evaluation of alternative splicing in the FAM190A gene
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The human FAM190A gene undergoes frequent alteration in human cancer, most commonly involving in-frame deletions in exon 9 or exons 9 & 10. These deletions form novel peptide sequences, serving as presumptive cancer-specific neo antigens. However, it remains elusive whether these in-frame deletions of FAM190A could induce oncogenic properties in vivo. In this study, we aimed to explore the functional significance of in-frame deletions in FAM190A genes. We generated two deletion mutant forms, FAM190AΔexon9 and FAM190AΔexon9&10, and examined their gain-of-function effects in vitro and in vivo. Global transcript profiling in NIH3T3 cells revealed that the transcripts displaying altered expression following introduction of FAM190AΔexon9 and FAM190AΔexon9&10 were significantly enriched for genes assigned to cellular movement and cell-to-cell signaling, respectively. Furthermore, ectopic expression of FAM190AΔexon9 and FAM190AΔexon9&10 induced in vivo tumor formation in nu/nu mice. Taken together, our results are the first to demonstrate the in vivo oncogenic properties of in-frame deletions in the FAM190A gene and indicate that these transcript variants might be clinically applicable as therapeutic targets in patients with cancer.
KeywordsFAM190A Alternative splicing Gain-of-function Neo antigens Xenograft
This work was supported by an Incheon National University research Grant (2018-0240).
Compliance with ethical standards
Conflict of interest
Sung Ung Kang and Joon Tae Park declare that they have no conflict of interest.
This study had been approved by the International Animal Care and Use Committee of Johns Hopkins Medicine (JHM) (protocol number: 20130112001).
Informed consent was obtained from all individual participants included in the study.