title: Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features.
abstract: Long noncoding RNAs (lncRNAs) represent a vast unexplored genetic space that may hold missing drivers of tumourigenesis, but few such "driver lncRNAs" are known. Until now, they have been discovered through changes in expression, leading to problems in distinguishing between causative roles and passenger effects. We here present a different approach for driver lncRNA discovery using mutational patterns in tumour DNA. Our pipeline, ExInAtor, identifies genes with excess load of somatic single nucleotide variants (SNVs) across panels of tumour genomes. Heterogeneity in mutational signatures between cancer types and individuals is accounted for using a simple local trinucleotide background model, which yields high precision and low computational demands. We use ExInAtor to predict drivers from the GENCODE annotation across 1112 entire genomes from 23 cancer types. Using a stratified approach, we identify 15 high-confidence candidates: 9 novel and 6 known cancer-related genes, including MALAT1, NEAT1 and SAMMSON. Both known and novel driver lncRNAs are distinguished by elevated gene length, evolutionary conservation and expression. We have presented a first catalogue of mutated lncRNA genes driving cancer, which will grow and improve with the application of ExInAtor to future tumour genome projects.
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Lanzós
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Carlevaro-Fita
authors.affiliation: Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, Barcelona, Spain.
authors.forename: Loris
authors.initials: L
authors.lastname: Mularoni
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Reverter
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Palumbo
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Rory
authors.initials: R
authors.lastname: Johnson
mesh_terms: D017398:Alternative Splicing; D014408:Biomarkers, Tumor; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D009857:Oncogenes; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding