Functional chromatin features are associated with structural mutations in cancer.

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Serval ID
serval:BIB_623AF785256E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional chromatin features are associated with structural mutations in cancer.
Journal
Bmc Genomics
Author(s)
Grzeda K.R., Royer-Bertrand B., Inaki K., Kim H., Hillmer A.M., Liu E.T., Chuang J.H.
ISSN
1471-2164 (Electronic)
ISSN-L
1471-2164
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
15
Pages
1013
Language
english
Notes
Publication types: Journal Article
Abstract
BACKGROUND: Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently in transcribed regions, while in other cancer types such as prostate, there is a consistent depletion of breakpoints in transcribed regions. Despite such regularity, little is understood about the mechanisms driving these effects. A few works have suggested that protein binding may be relevant, e.g. in studies of androgen receptor binding and active chromatin in specific cell types. We hypothesized that this behavior might be general, i.e. that correlation between protein-DNA binding (and open chromatin) and breakpoint locations is common across divergent cancers.
RESULTS: We investigated this hypothesis by comprehensively analyzing the relationship among 457 ENCODE protein binding ChIP-seq experiments, 125 DnaseI and 24 FAIRE experiments, and 14,600 SMs from 8 diverse cancer datasets covering 147 samples. In most cancers, including breast and ovarian, we found enrichment of protein binding and open chromatin in the vicinity of SM breakpoints at distances up to 200 kb. Furthermore, for all cancer types we observed an enhanced enrichment in regions distant from genes when compared to regions proximal to genes, suggesting that the SM-induction mechanism is independent from the bias of DSBs to occur near transcribed regions. We also observed a stronger effect for sites with more than one protein bound.
CONCLUSIONS: Protein binding and open chromatin state are associated with nearby SM breakpoints in many cancer datasets. These observations suggest a consistent mechanism underlying SM locations across different cancers.
Pubmed
Web of science
Open Access
Yes
Create date
27/12/2014 9:24
Last modification date
20/08/2019 14:19
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