A Pan-cancer Transcriptome Analysis Reveals Pervasive Regulation through Alternative Promoters

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Demircioglu, D (Autor) Outra; Cukuroglu, E (Autor) Outra; Kindermans, M (Autor) Outra; Nandi, T (Autor) Outra; Calabrese, C (Autor) Outra; Nuno A Fonseca (Autor) FEUP; Kahles, A (Autor) Outra; Kjong Van Lehmann, (Autor) Outra; Stegle, O (Autor) Outra; Brazma, A (Autor) Outra; Brooks, AN (Autor) Outra; Ratsch, G (Autor) Outra; Tan, P (Autor) Outra; Goke, J (Autor) Outra

Revista

Título: Cell

Vol. 178

Páginas: 1465-+

ISSN: 0092-8674

Editora: Elsevier

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 10 Citações

Outras Informações

ID Authenticus: P-00R-0HS

DOI: 10.1016/j.cell.2019.08.018

Abstract (EN): Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. However, while a global change in transcription is recognized as a defining feature of cancer, the contribution of alternative promoters still remains largely unexplored. Here, we infer active promoters using RNA-seq data from 18,468 cancer and normal samples, demonstrating that alternative promoters are a major contributor to context-specific regulation of transcription. We find that promoters are deregulated across tissues, cancer types, and patients, affecting known cancer genes and novel candidates. For genes with independently regulated promoters, we demonstrate that promoter activity provides a more accurate predictor of patient survival than gene expression. Our study suggests that a dynamic landscape of active promoters shapes the cancer transcriptome, opening new diagnostic avenues and opportunities to further explore the interplay of regulatory mechanisms with transcriptional aberrations in cancer.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 30