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

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ID: 40423
2019
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Abstract
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.
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demircioglu2019acell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Demircioğlu, Deniz;Cukuroglu, Engin;Kindermans, Martin;Nandi, Tannistha;Calabrese, Claudia;Fonseca, Nuno A;Kahles, André;Lehmann, Kjong-Van;Stegle, Oliver;Brazma, Alvis;Brooks, Angela N;Rätsch, Gunnar;Tan, Patrick;Göke, Jonathan;
Journal Cell
Year 2019
DOI
S0092-8674(19)30906-7
URL
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