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Updated: Oct 10, 2025

Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by Capillary Isoelectric Focusing Method
Published on: September 19, 2018
Probing Isoform Switching Events in Various Cancer Types: Lessons From Pan-Cancer Studies
Tülay Karakulak1,2,3, Holger Moch2,4, Christian von Mering1,3
1Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Abstract:
Alternative splicing is an essential regulatory mechanism for gene expression in mammalian cells contributing to protein, cellular, and species diversity. In cancer, alternative splicing is frequently disturbed, leading to changes in the expression of alternatively spliced protein isoforms. Advances in sequencing technologies and analysis methods led to new insights into the extent and functional impact of disturbed alternative splicing events. In this review, we give a brief overview of the molecular mechanisms driving alternative splicing, highlight the function of alternative splicing in healthy tissues and describe how alternative splicing is disrupted in cancer. We summarize current available computational tools for analyzing differential transcript usage, isoform switching events, and the pathogenic impact of cancer-specific splicing events. Finally, the strategies of three recent pan-cancer studies on isoform switching events are compared. Their methodological similarities and discrepancies are highlighted and lessons learned from the comparison are listed. We hope that our assessment will lead to new and more robust methods for cancer-specific transcript detection and help to produce more accurate functional impact predictions of isoform switching events.
Insights
Alternative splicing regulates gene expression and protein diversity. In cancer, altered splicing creates distinct protein isoforms, impacting disease progression and therapeutic strategies.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Alternative splicing is a key regulator of gene expression in mammals, generating protein diversity.
- Dysregulation of alternative splicing is a hallmark of cancer, leading to altered protein isoform expression.
- Recent advances in sequencing and analysis have revealed the extent and impact of aberrant splicing in cancer.
Purpose of the Study:
- To review the molecular mechanisms of alternative splicing.
- To describe the role of alternative splicing in healthy tissues and its disruption in cancer.
- To compare computational tools and pan-cancer study strategies for analyzing splicing events.
Main Methods:
- Literature review of molecular mechanisms and functions of alternative splicing.
- Summary of computational tools for analyzing differential transcript usage and isoform switching.
- Comparative analysis of recent pan-cancer studies on isoform switching events.
Main Results:
- Alternative splicing contributes to protein, cellular, and species diversity.
- Cancer-specific splicing events lead to pathogenic protein isoforms.
- Comparison of pan-cancer studies highlights methodological similarities and discrepancies.
Conclusions:
- Understanding disrupted alternative splicing in cancer is crucial for diagnostics and therapeutics.
- Development of robust methods for cancer-specific transcript detection is needed.
- Improved prediction of functional impacts of isoform switching events will advance cancer research.
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