A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference.
Dina CramerLuis SerranoMartin H SchaeferPublished in: eLife (2016)
Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position, but the sources of this variability are not known. CNA number and length are linked to patient survival, suggesting clinical relevance. We have identified genes that tend to be mutated in samples that have 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 investigated how the epigenome of the tissue-of-origin influences the position of CNA breakpoints and the properties of the resulting CNAs. We found that the presence of heterochromatin in the tissue-of-origin contributes to the recurrence and length of CNAs in the respective cancer type.
Keyphrases
- copy number
- genome wide
- dna methylation
- mitochondrial dna
- dna repair
- gene expression
- dna damage
- bioinformatics analysis
- genome wide identification
- small molecule
- free survival
- papillary thyroid
- physical activity
- dna damage response
- squamous cell carcinoma
- drinking water
- genome wide analysis
- young adults
- mass spectrometry
- high resolution
- atomic force microscopy
- childhood cancer