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Nat Commun. 2014 Apr 9;5:3644. doi: 10.1038/ncomms4644.

Processed pseudogenes acquired somatically during cancer development.

Author information

1
Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
2
Lungs for Living Research Centre, Rayne Institute, University College London, London WC1E 6JF, UK.
3
1] Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK [2] University of Cambridge, Cambridge CB2 0XY, UK.
4
Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
5
Addenbrooke's NHS Foundation Trust, Cambridge CB2 0QQ, UK.
6
Children's Brain Tumour Research Centre, University of Nottingham, Nottingham NG7 2UH, UK.
7
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
8
Institute for Cancer Research, Sutton, London SM2 5NG, UK.
9
Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
10
1] Lungs for Living Research Centre, Rayne Institute, University College London, London WC1E 6JF, UK [2] Royal National Orthopaedic Hospital, Middlesex HA7 4LP, UK.
11
Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.
12
Department of Pathology, Memorial-Sloan-Kettering Cancer Center, New York, New York 10065, USA.
13
1] Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia [2] Department of Gastroenterology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria 3050, Australia.
14
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27713, USA.
15
UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
16
1] Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK [2] Addenbrooke's NHS Foundation Trust, Cambridge CB2 0QQ, UK.
17
1] Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK [2] University of Cambridge, Cambridge CB2 0XY, UK [3] Addenbrooke's NHS Foundation Trust, Cambridge CB2 0QQ, UK.

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.

PMID:
24714652
PMCID:
PMC3996531
DOI:
10.1038/ncomms4644
[Indexed for MEDLINE]
Free PMC Article

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