title: A pan-cancer analysis of alternative splicing events reveals novel tumor-associated splice variants of matriptase.
abstract: High-throughput transcriptome sequencing allows identification of cancer-related changes that occur at the stages of transcription, pre-messenger RNA (mRNA), and splicing. In the current study, we devised a pipeline to predict novel alternative splicing (AS) variants from high-throughput transcriptome sequencing data and applied it to large sets of tumor transcriptomes from The Cancer Genome Atlas (TCGA). We identified two novel tumor-associated splice variants of matriptase, a known cancer-associated gene, in the transcriptome data from epithelial-derived tumors but not normal tissue. Most notably, these variants were found in 69% of lung squamous cell carcinoma (LUSC) samples studied. We confirmed the expression of matriptase AS transcripts using quantitative reverse transcription PCR (qRT-PCR) in an orthogonal panel of tumor tissues and cell lines. Furthermore, flow cytometric analysis confirmed surface expression of matriptase splice variants in chinese hamster ovary (CHO) cells transiently transfected with cDNA encoding the novel transcripts. Our findings further implicate matriptase in contributing to oncogenic processes and suggest potential novel therapeutic uses for matriptase splice variants.
authors.affiliation: BC Cancer Agency, Genome Sciences Center, Vancouver, British Columbia, Canada. ; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Daryanaz
authors.initials: D
authors.lastname: Dargahi
authors.affiliation: Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Swayze
authors.affiliation: Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: Leanna
authors.initials: L
authors.lastname: Yee
authors.affiliation: Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bergqvist
authors.affiliation: Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Hedberg
authors.affiliation: BC Cancer Agency, Genome Sciences Center, Vancouver, British Columbia, Canada.
authors.forename: Alireza
authors.initials: A
authors.lastname: Heravi-Moussavi
authors.affiliation: Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: Edie M
authors.initials: EM
authors.lastname: Dullaghan
authors.affiliation: Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: Dercho
authors.affiliation: BC Cancer Agency, Genome Sciences Center, Vancouver, British Columbia, Canada.
authors.forename: Jianghong
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. ; Center for Drug Research and Development (CDRD), Vancouver, British Columbia, Canada.
authors.forename: John S
authors.initials: JS
authors.lastname: Babcook
authors.affiliation: BC Cancer Agency, Genome Sciences Center, Vancouver, British Columbia, Canada. ; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Steven Jm
authors.initials: SJ
authors.lastname: Jones
keywords: RNA sequencing; alternative splicing; de novo assembly; epithelial tumors; matriptase