Previous large-scale sequencing projects have identified many putative cancer genes, but most efforts have concentrated on mutations and copy-number alterations in protein-coding genes, mainly using wholeexome sequencing and single-nucleotide polymorphism arrays 1-4. Whole-genome sequencing has made it possible to systematically survey non-coding regions for potential driver events, including single-nucleotide variants (SNVs), small insertions and deletions (indels) and larger structural variants. Whole-genome sequencing enables the precise localization of structural variant breakpoints and connections between distinct genomic loci (juxtapositions). Although previous whole-genome sequencing analyses of modestly sized cohorts have revealed candidate non-coding regulatory driver events 8-15 ,

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.