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Updated: Apr 16, 2026
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Transcriptome-wide identification and study of cancer-specific splicing events across multiple tumors
Yihsuan S Tsai1, Daniel Dominguez2, Shawn M Gomez1,2,3,4
1Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Abstract:
Dysregulation of alternative splicing (AS) is one of the molecular hallmarks of cancer, with splicing alteration of numerous genes in cancer patients. However, studying splicing mis-regulation in cancer is complicated by the large noise generated from tissue-specific splicing. To obtain a global picture of cancer-specific splicing, we analyzed transcriptome sequencing data from 1149 patients in The Cancer Genome Atlas project, producing a core set of AS events significantly altered across multiple cancer types. These cancer-specific AS events are highly conserved, are more likely to maintain protein reading frame, and mainly function in cell cycle, cell adhesion/migration, and insulin signaling pathways. Furthermore, these events can serve as new molecular biomarkers to distinguish cancer from normal tissues, to separate cancer subtypes, and to predict patient survival. We also found that most genes whose expression is closely associated with cancer-specific splicing are key regulators of the cell cycle. This study uncovers a common set of cancer-specific AS events altered across multiple cancers, providing mechanistic insight into how splicing is mis-regulated in cancers.
Insights
Alternative splicing (AS) alterations are common in cancer. This study identified conserved, cancer-specific AS events across multiple cancer types, revealing their role in cell cycle regulation and potential as biomarkers.
Area of Science:
- Molecular Biology
- Cancer Genomics
- Bioinformatics
Background:
- Alternative splicing (AS) dysregulation is a hallmark of cancer.
- Tissue-specific splicing introduces noise, complicating the study of cancer-specific splicing alterations.
Purpose of the Study:
- To identify a core set of alternative splicing events significantly altered across multiple cancer types.
- To understand the functional roles and potential biomarker applications of cancer-specific AS events.
Main Methods:
- Analysis of transcriptome sequencing data from 1149 cancer patients via The Cancer Genome Atlas (TCGA) project.
- Identification and characterization of conserved, cancer-specific AS events.
- Correlation analysis between gene expression and splicing alterations.
Main Results:
- A core set of cancer-specific AS events, conserved across multiple cancer types, was identified.
- These AS events are enriched in pathways regulating cell cycle, cell adhesion/migration, and insulin signaling.
- Cancer-specific AS events demonstrated potential as biomarkers for cancer detection, subtyping, and survival prediction.
- Genes strongly associated with cancer-specific splicing are frequently key regulators of the cell cycle.
Conclusions:
- This study uncovers a common set of cancer-specific AS events prevalent across diverse cancers.
- These findings provide mechanistic insights into splicing mis-regulation in cancer and highlight the utility of AS events as biomarkers.
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