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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

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, Peter Van Loo

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. More... »

PAGES

1221

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-01355-0

    DOI

    http://dx.doi.org/10.1038/s41467-017-01355-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092389974

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29089486


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