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

  • PCAWG Drivers and Functional Interpretation Group
  • , PCAWG Consortium
  • University of Bern
  • German Cancer Research Center
  • Department of Cell and Developmental Biology
  • Pompeu Fabra University
  • Hospital del Mar
  • Aarhus University
  • Wellcome Trust Sanger Institute
  • University of Texas MD Anderson Cancer Center
  • Jackson Laboratory
  • Baylor College of Medicine
  • University of Toronto
  • Ontario Institute for Cancer Research
  • Broad Institute
  • Dana-Farber Cancer Institute
  • Harvard University
  • RIKEN
  • Technical University of Denmark
  • University of Copenhagen
  • University of Cambridge
  • Heidelberg University 
  • Korea Advanced Institute of Science and Technology
  • Institute for Research in Biomedicine
  • Cornell University
  • Uppsala University
  • Barcelona Supercomputing Center (BSC)
  • University of Queensland
  • University of Porto
  • European Molecular Biology Laboratory
  • University of Milan - Bicocca
  • Peter Maccallum Cancer Centre
  • University of Melbourne
  • Princeton University
  • Yale University
  • Massachusetts General Hospital
  • University of California at Santa Cruz
  • Stanford University
  • University of Texas Health Science Center at Houston
  • Simon Fraser University
  • Memorial Sloan-Kettering Cancer Center
  • Swiss Federal Institute of Technology Zurich
  • Swiss Institute of Bioinformatics
  • University of Zurich
  • Unknown

Research output: Contribution to journal › Journal Article › peer-review

165 Scopus citations

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 - 01 12 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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