A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

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Arquivos
art_CHEN_A_PanCancer_Analysis_of_Enhancer_Expression_in_Nearly_2018.PDF (4.55 MB)
Citações na Scopus
198
Tipo de produção
article
Data de publicação
2018
Editora
CELL PRESS
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
CHEN, Han
LI, Chunyan
PENG, Xinxin
ZHOU, Zhicheng
WEINSTEIN, John N.
LIANG, Han
Autor de Grupo de pesquisa
Canc Genome Atlas Res Network
Editores
Coordenadores
Organizadores
Citação
CELL, v.173, n.2, p.386-399.e12, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on ""chromatin-state'' to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer similar to 140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/30108
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - ODS/03