TY - JOUR
T1 - Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
AU - PCAWG Drivers and Functional Interpretation Group
AU - PCAWG Consortium
AU - Carlevaro-Fita, Joana
AU - Lanzós, Andrés
AU - Feuerbach, Lars
AU - Hong, Chen
AU - Mas-Ponte, David
AU - Pedersen, Jakob Skou
AU - Johnson, Rory
AU - Abascal, Federico
AU - Amin, Samirkumar B.
AU - Bader, Gary D.
AU - Barenboim, Jonathan
AU - Beroukhim, Rameen
AU - Bertl, Johanna
AU - Boroevich, Keith A.
AU - Brunak, Søren
AU - Campbell, Peter J.
AU - Chakravarty, Dimple
AU - Chan, Calvin Wing Yiu
AU - Chen, Ken
AU - Choi, Jung Kyoon
AU - Deu-Pons, Jordi
AU - Dhingra, Priyanka
AU - Diamanti, Klev
AU - Fink, J. Lynn
AU - Fonseca, Nuno A.
AU - Frigola, Joan
AU - Gambacorti-Passerini, Carlo
AU - Garsed, Dale W.
AU - Gerstein, Mark
AU - Getz, Gad
AU - Gonzalez-Perez, Abel
AU - Guo, Qianyun
AU - Gut, Ivo G.
AU - Haan, David
AU - Hamilton, Mark P.
AU - Haradhvala, Nicholas J.
AU - Harmanci, Arif O.
AU - Helmy, Mohamed
AU - Herrmann, Carl
AU - Hess, Julian M.
AU - Hobolth, Asger
AU - Hodzic, Ermin
AU - Hornshøj, Henrik
AU - Isaev, Keren
AU - Izarzugaza, Jose M.G.
AU - Johnson, Todd A.
AU - Juul, Malene
AU - Juul, Randi Istrup
A2 - Brazma, Alvis
A2 - Viksna, Juris
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85079071080
U2 - 10.1038/s42003-019-0741-7
DO - 10.1038/s42003-019-0741-7
M3 - Article
C2 - 32024996
AN - SCOPUS:85079071080
SN - 2399-3642
VL - 3
SP - 1
EP - 16
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 56
ER -
SDG 3 Good Health and Well-being