A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference
- The Barcelona Institute of Science and Technology, Spain
Abstract
Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position. CNA number and length are linked to patient survival suggesting clinical relevance. However, the sources of this variability are not known. We have identified genes that tend to be mutated in samples having few or many CNAs, which we term CONIM genes (COpy Number Instability Modulators). CONIM proteins cluster into a densely connected subnetwork of physical interactions and many of them are epigenetic modifiers. Therefore, we investigate how the epigenome of the tissue-of-origin influences the position of CNA breakpoints and the properties of the resulting CNAs. We find that the presence of heterochromatin in the tissue-of-origin contributes to the recurrence and length of CNAs in the respective cancer type.
Data availability
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HIPPIE protein-protein interactionsPublicly available at the Human Integrated Protein-Protein Interaction rEference website.
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Chromatin state model (18 states)Publicly available at NIH Roadmap Epigenomics Mapping Consortium.
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Histone ChIP-seq peaksPublicly available at NIH Roadmap Epigenomics Mapping Consortium.
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RNA expression (RNAseq)Publicly available at NIH Roadmap Epigenomics Mapping Consortium.
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SNP6 focal copy altered segmentsPublicly available at the Broad Institute website.
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Illumina HiSeq copy number dataPublicly available at the Broad Institute website.
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SNP6 recurrent copy number alterations (GISTIC2)Publicly available at the Broad Institute website.
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Mutation dataPublicly available at the Broad Institute website.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SCHAÂ 1933/1-1)
- Martin H Schaefer
European Commission (HEALTH-F4-2011-278568)
- Luis Serrano
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Cramer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference
eLife 5:e16519.
https://doi.org/10.7554/eLife.16519
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