TY - JOUR
T1 - FACER
T2 - Comprehensive molecular and functional characterization of epigenetic chromatin regulators
AU - Lu, Jianping
AU - Xu, Juan
AU - Li, Junyi
AU - Pan, Tao
AU - Bai, Jing
AU - Wang, Liqiang
AU - Jin, Xiyun
AU - Lin, Xiaoyu
AU - Zhang, Yunpeng
AU - Li, Yongsheng
AU - Li, Xia
AU - Sahni, Nidhi
N1 - Publisher Copyright:
© The Author(s)
PY - 2018/11/2
Y1 - 2018/11/2
N2 - Epigenetic alterations, a well-recognized cancer hallmark, are driven by chromatin regulators (CRs). However, little is known about the extent of CR deregulation in cancer, and less is known about their common and specialized roles across various cancers. Here, we performed genome-wide analyses and constructed molecular signatures and network profiles of functional CRs in over 10 000 tumors across 33 cancer types. By integration of DNA mutation, genome-wide methylation, transcriptional/post-transcriptional regulation, and protein interaction networks with clinical outcomes, we identified CRs associated with cancer subtypes and clinical prognosis as potential oncogenic drivers. Comparative network analysis revealed principles of CR regulatory specificity and functionality. In addition, we identified common and specific CRs by assessing their prevalence across cancer types. Common CRs tend to be histone modifiers and chromatin remodelers with fundamental roles, whereas specialized CRs are involved in context-dependent functions. Finally, we have made a user-friendly web interface-FACER (Functional Atlas of Chromatin Epigenetic Regulators) available for exploring clinically relevant CRs for the development of CR biomarkers and therapeutic targets. Our integrative analysis reveals specific determinants of CRs across cancer types and presents a resource for investigating disease-associated CRs.
AB - Epigenetic alterations, a well-recognized cancer hallmark, are driven by chromatin regulators (CRs). However, little is known about the extent of CR deregulation in cancer, and less is known about their common and specialized roles across various cancers. Here, we performed genome-wide analyses and constructed molecular signatures and network profiles of functional CRs in over 10 000 tumors across 33 cancer types. By integration of DNA mutation, genome-wide methylation, transcriptional/post-transcriptional regulation, and protein interaction networks with clinical outcomes, we identified CRs associated with cancer subtypes and clinical prognosis as potential oncogenic drivers. Comparative network analysis revealed principles of CR regulatory specificity and functionality. In addition, we identified common and specific CRs by assessing their prevalence across cancer types. Common CRs tend to be histone modifiers and chromatin remodelers with fundamental roles, whereas specialized CRs are involved in context-dependent functions. Finally, we have made a user-friendly web interface-FACER (Functional Atlas of Chromatin Epigenetic Regulators) available for exploring clinically relevant CRs for the development of CR biomarkers and therapeutic targets. Our integrative analysis reveals specific determinants of CRs across cancer types and presents a resource for investigating disease-associated CRs.
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U2 - 10.1093/nar/gky679
DO - 10.1093/nar/gky679
M3 - Article
C2 - 30102398
AN - SCOPUS:85056287592
SN - 0305-1048
VL - 46
SP - 10019
EP - 10033
JO - Nucleic acids research
JF - Nucleic acids research
IS - 19
ER -