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Processed pseudogenes acquired somatically during cancer development

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms4644

2041-1723

Susanna L. Cooke, Adam Shlien, John L. Marshall, Christodoulos Pipinikas, Sancha Martin, José M. C. Tubío, Yilong Li, Andrew Menzies, Laura Mudie, Manasa Ramakrishna, Lucy Yates, Helen Davies, Niccolò Bolli, Graham R. Bignell, Patrick 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 A. Iacobuzio‐Donahue, Thomas Santarius, Richard G. Grundy, David Malkin, Mel Greaves, Nikhil C. Munshi, Adrienne M. Flanagan, David D.L. Bowtell, Sancha Martin, Denis Larsimont, Jorge S. Reis‐Filho, Alex Boussioutas, Jack A. Taylor, Neil Hayes, Sam M. Janes, P. Andrew Futreal, Michael R. Stratton, Ultan McDermott, Peter J. Campbell, Elena Provenzano, Marc J. van de Vijver, Andrea L. Richardson, Colin A. Purdie, Sarah E. Pinder, Gaëtan Mac Grogan, Anne Vincent‐Salomon, Denis Larsimont, Dorthe Grabau, Torill Sauer, Øystein Garred, Anna Ehinger, Gert G. Van den Eynden, Carolien H. M. van Deurzen, Roberto Salgado, Jane E. Brock, Sunil R. Lakhani, Dilip D. Giri, Laurent Arnould, Jocelyne Jacquemier, Isabelle Treilleux, Carlos Caldas, Suet‐Feung Chin, Aquila Fatima, Alastair M. Thompson, Alasdair Stenhouse, John A. Foekens, John W.M. Martens, Anieta M. Sieuwerts, Arjen Brinkman, Henk G. Stunnenberg, Paul N. Span, Fred C.G.J. Sweep, Christine Desmedt, Christos Sotiriou, Gilles Thomas, Annegein Broeks, Anita Langerød, Samuel Aparício, Peter T. Simpson, Laura van ′t Veer, Jórunn E. Eyfjörd, Hólmfríður Hilmarsdóttir, Jón G. Jónasson, Anne‐Lise Børresen‐Dale, Ming Ta Michael Lee, Bernice H. Wong, Benita Kiat Tee Tan, Gerrit K. Hooijer,

Genomics and Phylogenetic Studies

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.