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Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
Entropy measures quantify global splicing disorders in cancer.
William Ritchie1, Samuel Granjeaud, Denis Puthier
1Université de Méditerranée, INSERM ERM 206, Technologies Avancées pour le Génome et Clinique, Marseille, France.
Plos Computational Biology
|March 29, 2008
Summary
Cancer tissues exhibit significant disruptions in normal alternative splicing, leading to increased disorder in gene expression. This splicing dysregulation, measured by Shannon
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Alternative splicing is a fundamental process in mammalian gene expression, producing multiple transcript variants from a single gene.
- Cancer is characterized by significant alterations in alternative splicing, often leading to aberrant splice forms.
- Previous research has focused on identifying cancer-specific splice variants, overlooking broader changes in normal isoform expression.
Purpose of the Study:
- To quantitatively assess the disruption of normal splice variant expression in cancer tissues.
- To compare the level of disorder (Shannon's entropy) in alternative splicing, polyadenylation, and transcription initiation between normal and cancer tissues.
- To investigate the relationship between splicing disruption, cellular proliferation, and the expression of splicing factors in cancer.
Main Methods:
- Analysis of isoform expression profiles in normal and cancer tissues from the same anatomical sites.
- Quantification of expression disorder using Shannon's entropy for different transcript variation types.
- Correlation analysis between splicing entropy gain, cellular proliferation estimates, and the abundance of splicing factor genes.
Main Results:
- Alternative splicing, but not polyadenylation or transcription initiation, showed significant entropy gains in 13 of 27 studied cancers.
- This gain in splicing entropy reflects a flattening of normal isoform expression profiles and correlates with increased cellular proliferation.
- Genes exhibiting the highest splicing entropy gain are enriched in splicing factors, suggesting a feedback mechanism.
Conclusions:
- The expression of normal splice variants is significantly disrupted in at least half of the studied cancers, representing a major splicing disorder.
- Splicing disruptions may arise from alterations in key splicing factors, which subsequently impact multiple target genes.
- This study provides the first quantitative estimate of splicing disruption in cancer, highlighting its prevalence and potential mechanisms.
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