A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference

Abstract
Data availability
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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

The following previously published data sets were used

(2012) HIPPIE protein-protein interactions
Publicly available at the Human Integrated Protein-Protein Interaction rEference website.

http://cbdm-01.zdv.uni-mainz.de/~mschaefer/hippie/hippie_v1_8.txt
1. Kundaje
2. A. et al.
(2015) Chromatin state model (18 states)
Publicly available at NIH Roadmap Epigenomics Mapping Consortium.

http://egg2.wustl.edu/roadmap/data/byFileType/chromhmmSegmentations/ChmmModels/core_K27ac/jointModel/final/all.mnemonics.bedFiles.tgz
1. Kundaje
2. A. et al.
(2015) Histone ChIP-seq peaks
Publicly available at NIH Roadmap Epigenomics Mapping Consortium.

http://egg2.wustl.edu/roadmap/data/byFileType/peaks/consolidated/narrowPeak/
1. Kundaje
2. A. et al.
(2015) RNA expression (RNAseq)
Publicly available at NIH Roadmap Epigenomics Mapping Consortium.

http://egg2.wustl.edu/roadmap/data/byDataType/rna/expression/57epigenomes.RPKM.pc.gz
1. Broad Institute TCGA Genome Data Analysis Center
(2014) SNP6 focal copy altered segments
Publicly available at the Broad Institute website.

http://gdac.broadinstitute.org/runs/analyses__2014_10_17/data/
1. Broad Institute TCGA Genome Data Analysis Center
(2015) Illumina HiSeq copy number data
Publicly available at the Broad Institute website.

http://gdac.broadinstitute.org/runs/stddata__2015_08_21/data/
1. Broad Institute TCGA Genome Data Analysis Center
(2015) SNP6 recurrent copy number alterations (GISTIC2)
Publicly available at the Broad Institute website.

http://gdac.broadinstitute.org/runs/analyses__2015_04_02/data/
1. Broad Institute TCGA Genome Data Analysis Center
(2014) Mutation data
Publicly available at the Broad Institute website.

http://gdac.broadinstitute.org/runs/stddata__2014_07_15/data/

Article and author information

Author details

Dina Cramer

EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.
Luis Serrano

EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain

For correspondence
luis.serrano@crg.eu

Competing interests
The authors declare that no competing interests exist.
Martin H Schaefer

EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain

For correspondence
martin.schaefer@crg.eu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7503-6364

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

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.