Dataset Information

Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer

ABSTRACT: 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. 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. Our results provide a rich resource of full-length transcriptome data for deeper studies of GC and other gastrointestinal malignancies.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stomach

DISEASE(S): Stomach Cancer

SUBMITTER: Dennis Kappei

LAB HEAD: Dennis Kappei

PROVIDER: PXD023373 | Pride | 2021-02-02

REPOSITORIES: pride

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			Action	DRS
	20161117_QPC_DK_Duke_PTan_MKN1_01a.raw	Raw
	20161117_QPC_DK_Duke_PTan_MKN1_01b.raw	Raw
	20161117_QPC_DK_Duke_PTan_MKN1_02a.raw	Raw
	20161117_QPC_DK_Duke_PTan_MKN1_02b.raw	Raw
	20161117_QPC_DK_Duke_PTan_MKN1_03a.raw	Raw

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Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer.

Huang Kie Kyon KK Huang Jiawen J Wu Jeanie Kar Leng JKL Lee Minghui M Tay Su Ting ST Kumar Vikrant V Ramnarayanan Kalpana K Padmanabhan Nisha N Xu Chang C Tan Angie Lay Keng ALK Chan Charlene C Kappei Dennis D Göke Jonathan J Tan Patrick P

Genome biology 20210122 1

<h4>Background</h4>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.<h4>Results</h4>We performed full-length transcriptome analysis across 10 GC cell lines covering four ...[more]

PMID: 33482911

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