Network perturbation by recurrent regulatory variants in cancer

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Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.
Publisher
PUBLIC LIBRARY SCIENCE
Issue Date
2017-03
Language
English
Article Type
Article
Keywords

TERT PROMOTER MUTATIONS; HUMAN CELL-TYPES; CHROMATIN INTERACTOME; DISEASE; GENES; PATHWAYS; DNA; MELANOMA; GENOMES; BINDING

Citation

PLOS COMPUTATIONAL BIOLOGY, v.13, no.3

ISSN
1553-734X
DOI
10.1371/journal.pcbi.1005449
URI
http://hdl.handle.net/10203/223455
Appears in Collection
BiS-Journal Papers(저널논문)
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