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A Pan-Cancer Catalogue of Cancer Driver Protein Interaction Interfaces
Eduard Porta-Pardo1, Luz Garcia-Alonso2, Thomas Hrabe1
1Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
Plos Computational Biology
|October 21, 2015
Summary
Cancer mutations at protein-protein interaction (PPI) interfaces are key drivers. This study identified 103 mutated PPI interfaces, revealing new cancer gene candidates and linking interface mutations to distinct tumor behaviors and patient outcomes.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Protein-protein interactions (PPIs) are crucial for cellular functions.
- The role of mutations at PPI interfaces in cancer development is understudied.
- Cancer genomes contain numerous somatic mutations impacting protein function.
Purpose of the Study:
- To systematically analyze mutation patterns at PPI interfaces across a large pan-cancer cohort.
- To identify PPI interfaces significantly enriched in somatic mutations.
- To explore the potential of these mutated interfaces as novel cancer drivers.
Main Methods:
- Utilized the e-Driver algorithm to analyze mutation distribution in PPI interfaces.
- Examined data from 10,028 proteins across 5,989 tumors from The Cancer Genome Atlas (TCGA).
- Integrated mutation data with clinical information.
Main Results:
- Identified 103 PPI interfaces enriched in somatic cancer mutations.
- 32 of these interfaces are in known cancer driver genes.
- 71 interfaces are in proteins not previously recognized as cancer drivers, despite implicated roles.
Conclusions:
- Mutations at PPI interfaces represent a significant, underappreciated aspect of cancer genomics.
- This study uncovers novel potential cancer driver genes through PPI interface mutation analysis.
- Specific interface mutations within the same gene can influence tumor behavior and patient prognosis.
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