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Probing Isoform Switching Events in Various Cancer Types: Lessons From Pan-Cancer Studies


Karakulak, Tülay; Moch, Holger; von Mering, Christian; Kahraman, Abdullah (2021). Probing Isoform Switching Events in Various Cancer Types: Lessons From Pan-Cancer Studies. Frontiers in Molecular Biosciences, 8:726902.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Biochemistry, Genetics and Molecular Biology (miscellaneous)
Life Sciences > Molecular Biology
Language:English
Date:2021
Deposited On:27 Dec 2021 05:03
Last Modified:27 May 2024 01:46
Publisher:Frontiers Research Foundation
ISSN:2296-889X
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fmolb.2021.726902
PubMed ID:34888349
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)