Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis

Joana Carlevaro-Fita, Andrés Lanzós, Lars Feuerbach, Chen Hong, David Mas-Ponte, Jakob Skou Pedersen, Rory Johnson*, Federico Abascal, Samirkumar B. Amin, Gary D. Bader, Jonathan Barenboim, Rameen Beroukhim, Johanna Bertl, Keith A. Boroevich, Søren Brunak, Peter J. Campbell, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon ChoiJordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, J. Lynn Fink, Nuno A. Fonseca, Joan Frigola, Carlo Gambacorti-Passerini, Dale W. Garsed, Mark Gerstein, Gad Getz, Abel Gonzalez-Perez, Qianyun Guo, Ivo G. Gut, David Haan, Mark P. Hamilton, Nicholas J. Haradhvala, Arif O. Harmanci, Mohamed Helmy, Carl Herrmann, Julian M. Hess, Asger Hobolth, Ermin Hodzic, Henrik Hornshøj, Keren Isaev, Jose M.G. Izarzugaza, Todd A. Johnson, Malene Juul, Randi Istrup Juul, Andre Kahles, Christof von Kalle, PCAWG Drivers and Functional Interpretation Group, PCAWG Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

151 Citations (Scopus)

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.

Original languageEnglish
Article number56
JournalCommunications Biology
Volume3
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

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