PT  - JOURNAL ARTICLE
AU  - Deniz Demircioğlu
AU  - Martin Kindermans
AU  - Tannistha Nandi
AU  - Engin Cukuroglu
AU  - Claudia Calabrese
AU  - Nuno A. Fonseca
AU  - Andre Kahles
AU  - Kjong Lehmann
AU  - Oliver Stegle
AU  - Alvis Brazma
AU  - Angela N. Brooks
AU  - Gunnar Rätsch
AU  - Patrick Tan
AU  - Jonathan Göke
AU  - on behalf of the PCAWG Transcriptome Working Group, and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
TI  - A Pan-Cancer Transcriptome Analysis Reveals Pervasive Regulation through Tumor-Associated Alternative Promoters
AID  - 10.1101/176487
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 176487
4099  - http://biorxiv.org/content/early/2018/05/02/176487.short
4100  - http://biorxiv.org/content/early/2018/05/02/176487.full
AB  - 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. While the role of promoters as driver elements in cancer has been recognized, the contribution of alternative promoters to regulation of the cancer transcriptome remains largely unexplored. Here we infer active promoters using RNA-Seq data from 1,188 cancer samples with matched whole genome sequencing data. We find that alternative promoters are a major contributor to context-specific regulation of isoform expression and that alternative promoters are frequently deregulated in cancer, affecting known cancer-genes and novel candidates. Our study suggests that a highly dynamic landscape of active promoters shapes the cancer transcriptome, opening many opportunities to further explore the interplay of regulatory mechanism and noncoding somatic mutations with transcriptional aberrations in cancer.