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

PCAWG Drivers and Functional Interpretation Group, PCAWG Consortium, 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 ChanKen Chen, Jung Kyoon Choi, Jordi 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, Abdullah Kahraman, Manolis Kellis, Ekta Khurana, Jaegil Kim, Jong K. Kim, Youngwook Kim, Jan Komorowski, Jan O. Korbel, Sushant Kumar, 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, Lauri A. Aaltonen, Adam Abeshouse, Hiroyuki Aburatani, David J. Adams, Nishant Agrawal, Keun Soo Ahn, Sung Min Ahn, Hiroshi Aikata, Rehan Akbani, Kadir C. Akdemir, Hikmat Al-Ahmadie, Sultan T. Al-Sedairy, Fatima Al-Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B. Alexandrov, Adrian Ally, Kathryn Alsop, Eva G. Alvarez, Fernanda Amary, Brice Aminou, Ole Ammerpohl, Matthew J. Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparicio, Elizabeth L. Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun Ichi Ariizumi, Joshua Armenia, Laurent Arnould, Sylvia Asa, Yassen Assenov, Gurnit Atwal, Sietse Aukema, J. Todd Auman, Miriam R.R. Aure, Philip Awadalla, Marta Aymerich, Adrian Baez-Ortega, Matthew H. Bailey, Peter J. Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E. Banks, Stefano Barbi, Andrew P. Barbour, Jill Barnholtz-Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolome, Claudio Bassi, Oliver F. Bathe, Daniel Baumhoer, Li Ding, Lucinda A. Fulton, Robert S. Fulton, Ramaswamy Govindan, Reyka Jayasinghe, Tim Ley, Christopher A. Miller, David Mutch, Michael C. Wendl

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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
StatePublished - Dec 1 2020

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