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, University of Bern researchers 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. The researchers 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.
Overview of the Cancer LncRNA Census
Rows represent the 122 CLC genes, columns represent 29 cancer types. Asterisks next to gene names indicate that they are predicted as drivers by PCAWG, based either on gene or promoter evidence (see Supplementary Data 1). Blue cells indicate evidence for the involvement of a given lncRNA in that cancer type. Left column indicates functional classification: tumour suppressor (TSG), oncogene (OG) or both (OG/TSG). Above and to the right, barplots indicate the total counts of each column/row. The piechart shows the fraction that CLC represents within GENCODE v24 lncRNAs. Note that 8 CLC genes are classified as “pseudogenes” by GENCODE. “nonCLC” refers to all other GENCODE-annotated lncRNAs, which are used as background in comparative analyses.
Availability – The Cancer LncRNA Census
Carlevaro-Fita J, Lanzós A, Feuerbach L, Hong C, Mas-Ponte D, Pedersen JS; PCAWG Drivers and Functional Interpretation Group, Johnson R, PCAWG Consortium. (2020) Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis. Commun Biol 3(1):56. [article]
The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. (2020) Pan-cancer analysis of whole genomes. Nature 578: 82–93 [article]