Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors

Jiqiu Cheng, Jonas Demeulemeester, David C. Wedge, Hans Kristian M. Vollan, Jason J. Pitt, Hege G. Russnes, Bina P. Pandey, Gro Nilsen, Silje Nord, Graham R. Bignell, Kevin P. White, Anne-Lise Børresen-Dale, Peter J. Campbell, Vessela N. Kristensen, Michael R. Stratton, Ole Christian Lingjærde, Yves Moreau and Peter Van Loo ()
Additional contact information
Jiqiu Cheng: University of Leuven
Jonas Demeulemeester: The Francis Crick Institute
David C. Wedge: Wellcome Trust Sanger Institute
Hans Kristian M. Vollan: Institute for Cancer Research, Oslo University Hospital Radiumhospitalet
Jason J. Pitt: University of Chicago
Hege G. Russnes: Institute for Cancer Research, Oslo University Hospital Radiumhospitalet
Bina P. Pandey: University of Leuven
Gro Nilsen: University of Oslo
Silje Nord: Institute for Cancer Research, Oslo University Hospital Radiumhospitalet
Graham R. Bignell: Wellcome Trust Sanger Institute
Kevin P. White: University of Chicago
Anne-Lise Børresen-Dale: Institute for Cancer Research, Oslo University Hospital Radiumhospitalet
Peter J. Campbell: Wellcome Trust Sanger Institute
Vessela N. Kristensen: Institute for Cancer Research, Oslo University Hospital Radiumhospitalet
Michael R. Stratton: Wellcome Trust Sanger Institute
Ole Christian Lingjærde: University of Oslo
Yves Moreau: University of Leuven
Peter Van Loo: The Francis Crick Institute

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2, are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01355-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01355-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01355-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().