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

PCAWG Drivers and Functional Interpretation Group, PCAWG Consortium

Research output: Contribution to journalArticlepeer-review

151 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 (US)
Article number56
JournalCommunications Biology
Volume3
Issue number1
DOIs
StatePublished - Dec 1 2020

Funding

We wish to thanks Julien Lagarde (CRG) for help and advice in bioinformatic analysis. We acknowledge Romina Garrido (CRG), Deborah Re (DBMR), Silvia Roesselet (DBMR) and Marianne Zahn (Inselspital) for administrative support. We thank Ivo Buchhalter (DKFZ) and Sandra Koser (DKFZ) for preprocessing the SNV and expression data for the integrated analysis. I\u00F1igo Martincorena (Sanger Institute) kindly provided the script for analysing driver prediction sensitivity. A.L. was supported by pre-doctoral fellowship FPU14/03371. This research was supported by the Swiss National Science Foundation through the National Centres for Competence in Research \u201CRNA & Disease\u201D, and by the Department of Medical Oncology of Inselspital. We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonised variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

Fingerprint

Dive into the research topics of 'Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis'. Together they form a unique fingerprint.

Cite this