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

Joana Carlevaro-Fita, Chen Hong, David Mas-Ponte, Jakob Skou Pedersen, 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 Choi, Jordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, Lars Feuerbach, 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, Rory Johnson, Todd A. Johnson, Malene Juul, Randi Istrup Juul, Andre Kahles, Abdullah Kahraman, Manolis Kellis, Ekta Khurana, Jaegil Kim, Jong K. Kim, Youngwook Kim, Jan Komorowski, Jan O. Korbel, Sushant Kumar, Andrés Lanzós, Erik Larsson, Michael S. Lawrence, Donghoon Lee, Kjong-Van Lehmann, Shantao Li, Xiaotong Li, Ziao Lin, Eric Minwei Liu, Lucas Lochovsky, Shaoke Lou, Tobias Madsen, Kathleen Marchal, Iñigo Martincorena, Alexander Martinez-Fundichely, Yosef E. Maruvka, Patrick D. McGillivray, William Meyerson, Ferran Muiños, Loris Mularoni, Hidewaki Nakagawa, Morten Muhlig Nielsen, Marta Paczkowska, Keunchil Park, Kiejung Park, Oriol Pich, Tirso Pons, Sergio Pulido-Tamayo, Benjamin J Raphael, Jüri Reimand, Iker Reyes-Salazar, Matthew A. Reyna, Esther Rheinbay, Mark A. Rubin, Carlota Rubio-Perez, Radhakrishnan Sabarinathan, S. Cenk Sahinalp, Gordon Saksena, Leonidas Salichos, Chris Sander, Steven E. Schumacher, Mark Shackleton, Ofer Shapira, Ciyue Shen, Raunak Shrestha, Shimin Shuai, Nikos Sidiropoulos, Lina Sieverling, Nasa Sinnott-Armstrong, Lincoln D. Stein, Joshua M. Stuart, David Tamborero, Grace Tiao, Tatsuhiko Tsunoda, Husen M. Umer, Liis Uusküla-Reimand, Alfonso Valencia, Miguel Vazquez, Lieven P. C. Verbeke, Claes Wadelius, Lina Wadi, Jiayin Wang, Jonathan Warrell, Sebastian M. Waszak, Joachim Weischenfeldt, David A. Wheeler, Guanming Wu, Jun Yu, Jing Zhang, Xuanping Zhang, Yan Zhang, Zhongming Zhao, Lihua Zou, Christian von Mering

OAI: oai:www.repository.cam.ac.uk:1810/317171 • DOI: 10.17863/CAM.64282

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.

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