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Alternative mRNA splicing in anthracycline-induced cardiomyopathy - a COG-ALTE03N1 report
Purnima Singh1,2, David K Crossman3, Changde Cheng4
1Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL, USA. purnimasingh@uabmc.edu.
Background:
Anthracycline-induced cardiomyopathy is a well-established adverse consequence in childhood cancer survivors. Altered mRNA expression in the peripheral blood has been found at the level of genes and pathways among anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. However, the role of aberrant alternative splicing in anthracycline-induced cardiomyopathy remains unexplored. The present study examined if transcript-specific events, due to alternative splicing occur in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy.
Methods:
Participants were anthracycline-exposed childhood cancer survivors with cardiomyopathy (cases) matched with anthracycline-exposed childhood cancer survivors without cardiomyopathy (controls; matched on primary cancer diagnosis, year of diagnosis, and race/ethnicity). mRNA sequencing was performed on total RNA from peripheral blood in 32 cases and 32 matched controls. Event-level splicing tool, rMATS (replicate Multivariate Analysis of Transcript Splicing) was used for quantitative profiling of alternative splicing events.
Results:
A total of 45 alternative splicing events in 36 genes were identified. Using a prioritization strategy to filter the alternative splicing events, intron retention in RPS24 and skipped exon of PFND5 showed differential expression of altered transcripts.
Conclusions:
We identified specific alternative splicing events in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Our findings suggest that differential alternative splicing events can provide additional insight into the peripheral blood transcriptomic landscape of anthracycline-induced cardiomyopathy.
Insights
This study explored alternative splicing in childhood cancer survivors, finding specific events in genes like RPS24 and PFND5. These splicing changes may offer new insights into anthracycline-induced cardiomyopathy.
Area of Science:
- Cardiology
- Genomics
- Oncology
Background:
- Anthracycline chemotherapy can cause cardiomyopathy in childhood cancer survivors.
- While altered mRNA expression is known, the role of alternative splicing in this condition is unclear.
- This study investigates alternative splicing events in survivors with and without cardiomyopathy.
Purpose of the Study:
- To determine if alternative splicing events occur in childhood cancer survivors exposed to anthracyclines.
- To identify specific transcript-level changes associated with anthracycline-induced cardiomyopathy.
Main Methods:
- Compared 32 childhood cancer survivors with cardiomyopathy (cases) to 32 matched survivors without cardiomyopathy (controls).
- Analyzed peripheral blood RNA using mRNA sequencing.
- Utilized the rMATS tool for quantitative profiling of alternative splicing events.
Main Results:
- Identified 45 alternative splicing events across 36 genes.
- Found differential expression of altered transcripts, specifically intron retention in RPS24 and skipped exon in PFND5.
- These events were prioritized for their potential significance.
Conclusions:
- Specific alternative splicing events were identified in childhood cancer survivors with and without anthracycline-induced cardiomyopathy.
- These findings suggest that alternative splicing analysis can enhance understanding of the peripheral blood transcriptomic landscape in this patient group.
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