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Unique genomic features and deeply-conserved functions of long non-coding RNAs in the Cancer LncRNA Census (CLC)

View ORCID ProfileJoana Carlevaro-Fita, View ORCID ProfileAndrés Lanzós, View ORCID ProfileLars Feuerbach, Chen Hong, View ORCID ProfileDavid Mas-Ponte, View ORCID ProfileJakob Skou Pedersen, Rory Johnson, On behalf of the PCAWG Drivers and Functional Interpretation Group and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
doi: https://doi.org/10.1101/152769
Joana Carlevaro-Fita
1Department of Clinical Research, University of Bern, 3008 Bern, Switzerland
2Department of Medical Oncology, Inselspital, University Hospital and University of Bern, 3010 Bern, Switzerland
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Andrés Lanzós
3Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain
4Universitat Pompeu Fabra (UPF), Barcelona, Spain
5Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Dr. Aiguader 88, 08003 Barcelona, Catalonia, Spain
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Lars Feuerbach
6Applied Bioinformatics, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany
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Chen Hong
6Applied Bioinformatics, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany
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David Mas-Ponte
3Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain
4Universitat Pompeu Fabra (UPF), Barcelona, Spain
5Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Dr. Aiguader 88, 08003 Barcelona, Catalonia, Spain
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Jakob Skou Pedersen
7Department for Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark
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Rory Johnson
1Department of Clinical Research, University of Bern, 3008 Bern, Switzerland
2Department of Medical Oncology, Inselspital, University Hospital and University of Bern, 3010 Bern, Switzerland
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Abstract

Long non-coding RNAs (lncRNAs) that drive tumorigenesis are a growing focus of cancer genomics studies. To facilitate further discovery, we have created the “Cancer LncRNA Census” (CLC), a manually-curated and strictly-defined compilation of lncRNAs with causative roles in cancer. CLC has two principle applications: first, as a resource for training and benchmarking de novo identification methods; and second, as a dataset for studying the fundamental properties of these genes.

CLC Version 1 comprises 122 lncRNAs implicated in 29 distinct cancers. LncRNAs are included based on functional or genetic evidence for causative roles in cancer progression. All belong to the GENCODE reference annotation, to enable integration across projects and datasets. For each entry, the evidence type, biological activity (oncogene or tumour suppressor), source reference and cancer type are recorded. Supporting its usefulness, CLC genes are significantly enriched amongst de novo predicted driver genes from PCAWG. CLC genes are distinguished from other lncRNAs by a series of features consistent with biological function, including gene length, high expression and sequence conservation of both exons and promoters. We identify a trend for CLC genes to be co-localised with known protein-coding cancer genes along the human genome. Finally, by integrating data from transposon-mutagenesis functional screens, we show that mouse orthologues of CLC genes tend also to be cancer genes.

Thus CLC represents a valuable resource for research into long non-coding RNAs in cancer. Their evolutionary and genomic properties have implications for understanding disease mechanisms and point to conserved functions across ~80 million years of evolution.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 25, 2017.
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Unique genomic features and deeply-conserved functions of long non-coding RNAs in the Cancer LncRNA Census (CLC)
Joana Carlevaro-Fita, Andrés Lanzós, Lars Feuerbach, Chen Hong, David Mas-Ponte, Jakob Skou Pedersen, Rory Johnson, On behalf of the PCAWG Drivers and Functional Interpretation Group and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
bioRxiv 152769; doi: https://doi.org/10.1101/152769
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Unique genomic features and deeply-conserved functions of long non-coding RNAs in the Cancer LncRNA Census (CLC)
Joana Carlevaro-Fita, Andrés Lanzós, Lars Feuerbach, Chen Hong, David Mas-Ponte, Jakob Skou Pedersen, Rory Johnson, On behalf of the PCAWG Drivers and Functional Interpretation Group and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
bioRxiv 152769; doi: https://doi.org/10.1101/152769

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