Processed pseudogenes acquired somatically during cancer development

Susanna L. Cooke, Adam Shlien, John Marshall, Christodoulos P. Pipinikas, Inigo Martincorena, Jose M.C. Tubio, Yilong Li, Andrew Menzies, Laura Mudie, Manasa Ramakrishna, Lucy Yates, Helen Davies, Niccolo Bolli, Graham R. Bignell, Patrick S. Tarpey, Sam Behjati, Serena Nik-Zainal, Elli Papaemmanuil, Vitor H. Teixeira, Keiran Raine, Sarah O’Meara, Maryam S. Dodoran, Jon W. Teague, Adam P. Butler, Christine Iacobuzio-Donahue, Thomas Santarius, Richard G. Grundy, David Malkin, Mel Greaves, Nikhil Munshi, Adrienne M. Flanagan, David Bowtell, Sancha Martin, Denis Larsimont, Jorge S. Reis-Filho, Alex Boussioutas, Jack A. Taylor, Neil D. Hayes, Sam M. Janes, P. Andrew Futreal, Michael R. Stratton, Ultan McDermott and Peter J. Campbell ()
Additional contact information
Susanna L. Cooke: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Adam Shlien: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
John Marshall: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Christodoulos P. Pipinikas: Lungs for Living Research Centre, Rayne Institute, University College London
Inigo Martincorena: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Jose M.C. Tubio: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Yilong Li: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Andrew Menzies: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Laura Mudie: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Manasa Ramakrishna: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Lucy Yates: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Helen Davies: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Niccolo Bolli: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Graham R. Bignell: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Patrick S. Tarpey: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Sam Behjati: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Serena Nik-Zainal: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Elli Papaemmanuil: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Vitor H. Teixeira: Lungs for Living Research Centre, Rayne Institute, University College London
Keiran Raine: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Sarah O’Meara: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Maryam S. Dodoran: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Jon W. Teague: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Adam P. Butler: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Christine Iacobuzio-Donahue: Johns Hopkins Medical Institutions
Thomas Santarius: Addenbrooke’s NHS Foundation Trust
Richard G. Grundy: Children’s Brain Tumour Research Centre, University of Nottingham
David Malkin: Hospital for Sick Children, University of Toronto
Mel Greaves: Institute for Cancer Research, Sutton
Nikhil Munshi: Dana-Farber Cancer Institute
Adrienne M. Flanagan: Lungs for Living Research Centre, Rayne Institute, University College London
David Bowtell: Peter MacCallum Cancer Centre
Sancha Martin: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Jorge S. Reis-Filho: Memorial-Sloan-Kettering Cancer Center
Alex Boussioutas: Peter MacCallum Cancer Centre
Jack A. Taylor: National Institute of Environmental Health Sciences, Research Triangle Park
Neil D. Hayes: UNC Lineberger Comprehensive Cancer Center, University of North Carolina
Sam M. Janes: Lungs for Living Research Centre, Rayne Institute, University College London
P. Andrew Futreal: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Michael R. Stratton: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Ultan McDermott: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton
Peter J. Campbell: Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5′ truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

Date: 2014
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DOI: 10.1038/ncomms4644

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