Abstract
Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
Highlights
Long non-coding RNAs are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles
As part of recent efforts to identify driver lncRNAs by the Drivers and Functional Interpretation Group (PCAWG-2-5-9-14) within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network ( PCAWG)[16,38], we discovered the need for a high-confidence reference set of cancer-related lncRNA genes, which we refer to as cancer lncRNAs
Our aim was to create a gene set with the greatest possible confidence, by eliminating the relatively large number of published cancer lncRNAs with as-yet unproven functional roles in disease processes
Summary
Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. It remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. The cast of genetic elements implicated in tumorigenesis has recently grown as diverse new classes of non-coding RNAs and regulatory features have been discovered. LncRNAs are >200 nt long transcripts with no protein-coding capacity Their evolutionary conservation and regulated expression, combined with a number of wellcharacterised examples, have together led to the view that lncRNAs are bona fide functional genes[6,7,8,9]. LincRNA-p21 acts as a downstream effector of p53 regulation through recruitment of the repressor hnRNP-K17
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