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

Nat Commun. 2016 Oct 25:7:13197. doi: 10.1038/ncomms13197.

Abstract

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 we 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. Our 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. We highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. Our study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Line, Tumor
  • Gene Dosage
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Genes, p53
  • Glutamate-Cysteine Ligase / genetics
  • Humans
  • Molecular Sequence Annotation
  • Mutation*
  • NF-E2-Related Factor 2 / genetics
  • Neoplasms / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Sequence Analysis, RNA
  • Transcription Factors / genetics
  • Transcriptome
  • Tumor Suppressor Protein p53 / genetics

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • GCLC protein, human
  • Glutamate-Cysteine Ligase