A pan-cancer transcriptome analysis reveals pervasive regulation through alternative promoters Journal Article
| Authors: | Demircioğlu, D.; Cukuroglu, E.; Kindermans, M.; Nandi, T.; Calabrese, C.; Fonseca, N. A.; Kahles, A.; Lehmann, K. V.; Stegle, O.; Brazma, A.; Brooks, A. N.; Rätsch, G.; Tan, P.; Göke, J. |
| Article Title: | A pan-cancer transcriptome analysis reveals pervasive regulation through alternative promoters |
| Abstract: | Alternative promoters are frequently used to regulate tissue- and cancer-specific transcription, and variation in promoter usage is associated with cancer patient survival. © 2019 Elsevier Inc. 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. © 2019 Elsevier Inc. |
| Keywords: | survival analysis; gene expression; computational biology; transcriptomics; genomics; transcriptional regulation; tcga; alternative promoters; cancer; rna sequencing |
| Journal Title: | Cell |
| Volume: | 178 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2019-09-05 |
| Start Page: | 1465 |
| End Page: | 1477.e17 |
| Language: | English |
| DOI: | 10.1016/j.cell.2019.08.018 |
| PUBMED: | 31491388 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2019 -- Source: Scopus |
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