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Título:	Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features
Autor/a:	Lanzos Camaioni, Andrés Arturo; Carlevaro-Fita, Joana; Mularoni, Loris; Reverter Comes, Ferran; Palumbo, Emilio; Guigó Serra, Roderic; Johnson, Rory
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.
Abstract:	We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017′, SEV-2012-0208. R.J. is supported by Ramón y Cajal RYC-2011-08851 and Plan Nacional BIO2011-27220. A.L. is supported by pre-doctoral fellowship FPU14/03371. This research was partly supported by the NCCR RNA & Disease funded by the Swiss National Science Foundation.
Materia(s):	-Cancer genomics -Long non-coding RNAs
Derechos:	© Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/
Tipo de documento:	Artículo Artículo - Versión publicada
Editor:	Nature Publishing Group
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