Network perturbation by recurrent regulatory variants in cancer

被引:5
|
作者
Jang, Kiwon [1 ]
Kim, Kwoneel [1 ]
Cho, Ara [2 ]
Lee, Insuk [2 ]
Choi, Jung Kyoon [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Daejeon, South Korea
[2] Yonsei Univ, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul, South Korea
关键词
TERT PROMOTER MUTATIONS; HUMAN CELL-TYPES; CHROMATIN INTERACTOME; DISEASE; GENES; PATHWAYS; DNA; MELANOMA; GENOMES; BINDING;
D O I
10.1371/journal.pcbi.1005449
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:15
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