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KMID : 0381120190410020193
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Genes and Genomics
2019 Volume.41 No. 2 p.193 ~ p.199
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Functional evaluation of alternative splicing in the FAM190A gene
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Kang Sung-Ung
Park Joon-Tae
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Abstract
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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.
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KEYWORD
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FAM190A, Alternative splicing, Gain-of-function, Neo antigens, Xenograft
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