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Title: Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer
Authors: Huang, Kie Kyon
Huang, Jiawen 
Wu, Jeanie Kar Leng 
Lee, Minghui 
Tay, Su Ting 
Kumar, Vikrant 
Ramnarayanan, Kalpana 
Padmanabhan, Nisha 
Xu, Chang 
Tan, Angie Lay Keng 
Chan, Charlene 
Kappei, Dennis 
Göke, Jonathan
Tan, Patrick 
Keywords: Alternative promoter
Alternative splicing
Gastric cancer
Issue Date: 22-Jan-2021
Publisher: BioMed Central Ltd
Citation: Huang, Kie Kyon, Huang, Jiawen, Wu, Jeanie Kar Leng, Lee, Minghui, Tay, Su Ting, Kumar, Vikrant, Ramnarayanan, Kalpana, Padmanabhan, Nisha, Xu, Chang, Tan, Angie Lay Keng, Chan, Charlene, Kappei, Dennis, Göke, Jonathan, Tan, Patrick (2021-01-22). Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer. Genome Biology 22 (1) : 44. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: Deregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform sequencing (Iso-Seq) and Illumina paired-end short-read RNA sequencing to comprehensively survey the transcriptome of gastric cancer (GC), a leading cause of global cancer mortality. Results: We performed full-length transcriptome analysis across 10 GC cell lines covering four major GC molecular subtypes (chromosomal unstable, Epstein-Barr positive, genome stable and microsatellite unstable). We identify 60,239 non-redundant full-length transcripts, of which > 66% are novel compared to current transcriptome databases. Novel isoforms are more likely to be cell line and subtype specific, expressed at lower levels with larger number of exons, with longer isoform/coding sequence lengths. Most novel isoforms utilize an alternate first exon, and compared to other alternative splicing categories, are expressed at higher levels and exhibit higher variability. Collectively, we observe alternate promoter usage in 25% of detected genes, with the majority (84.2%) of known/novel promoter pairs exhibiting potential changes in their coding sequences. Mapping these alternate promoters to TCGA GC samples, we identify several cancer-associated isoforms, including novel variants of oncogenes. Tumor-specific transcript isoforms tend to alter protein coding sequences to a larger extent than other isoforms. Analysis of outcome data suggests that novel isoforms may impart additional prognostic information. Conclusions: Our results provide a rich resource of full-length transcriptome data for deeper studies of GC and other gastrointestinal malignancies. © 2021, The Author(s).
Source Title: Genome Biology
ISSN: 1474-7596
DOI: 10.1186/s13059-021-02261-x
Rights: Attribution 4.0 International
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