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A practical framework and online tool for mutational signature analyses show inter-tissue variation and driver
Andrea Degasperi1,2,3, Tauanne Dias Amarante1,2,3, Jan Czarnecki1,2,3
1MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
Nature Cancer
|March 3, 2020
Summary
This study introduces a new framework for analyzing mutational signatures in cancer. The research identified new rearrangement signatures and emphasized the importance of multiple data sources for accurate tumor classification.
Area of Science:
- Genomics
- Cancer Research
- Bioinformatics
Background:
- Mutational signatures are crucial for understanding cancer development.
- Existing analysis frameworks can be enhanced for greater accuracy and utility.
- Identifying novel mutational patterns can reveal new insights into tumorigenesis.
Purpose of the Study:
- To present an enhanced, practical framework for mutational signature analysis.
- To identify and characterize novel mutational signatures in human cancers.
- To explore the inter-organ variability of mutational signatures and their impact on tumor classification.
Main Methods:
- Analysis of whole genome sequencing (WGS) data from 3,107 primary and 3,096 metastatic cancers across 21 organs.
- Development and application of an enhanced computational framework for mutational signature identification.
- Comparative analysis of mutational signatures between primary and metastatic tumors and across different organs.
Main Results:
- Discovery of nine novel rearrangement mutational signatures.
- Demonstration of significant inter-organ variability in mutational signature profiles.
- Established a link between high genomic instability signatures and TP53 dysregulation.
- Highlighted the impact of signature uncertainty on tumor classification.
Conclusions:
- The enhanced framework provides a robust approach to mutational signature analysis.
- Accurate tumor stratification necessitates the use of multiple orthogonal mutational signature data.
- The Signal web tool (https://signal.mutationalsignatures.com) offers a valuable resource for cancer mutational signature research and analysis.
