FACER: comprehensive molecular and functional characterization of epigenetic chromatin regulators.
Nucleic Acids Res
; 46(19): 10019-10033, 2018 11 02.
Article
em En
| MEDLINE
| ID: mdl-30102398
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Regulação Neoplásica da Expressão Gênica
/
Metilação de DNA
/
Neoplasias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China