Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events

Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here researchers from the University of Gothenburg make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Their screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways. The associations are often highly reproducible across cancer types, and while many lncRNAs are co-expressed with their protein-coding hosts or neighbours, some are intergenic and independent. The researchers highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. This study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers.

Associations between driver mutations and lncRNA expression levels


(a) 13,307 lncRNAs were tested for associations with key mutational events for coding genes. Only associations replicated in more than one cancer type were further considered. 189 such consistent associations (right boxes with arrows) were found for 21 mutational events shown here, compared with 0 in randomized data. (b) Dependencies between associated lncRNAs and proximal coding genes (closest neighbours on either side as well as any coding gene within 100 kb).  (c) Expression of the β-catenin target NKD1 and its intronic antisense transcript RP11-401P9.6 in CTNNB1 mutated compared with wild type tumours. (d) Reduced expression of LINC01021 and RP3-510D11.2 in TP53 mutated compared with wild type tumours. (e) p53-dependent expression of RP11-115D19.1 in TCGA tumours (left) as well as in HCT116 colon carcinoma cells (TP53 +/+ or −/−) treated with the p53-activating agent Nutlin-3.

Ashouri A, Sayin VI, Van den Eynden J, Singh SX, Papagiannakopoulos T, Larsson E. (2016) Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events. Nature Comm [Epub ahead of print]. [article]

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