Processed pseudogenes acquired somatically during cancer development

Cooke, S. L. et al. (2014) Processed pseudogenes acquired somatically during cancer development. Nature Communications, 5, 3644. (doi: 10.1038/ncomms4644) (PMID:24714652) (PMCID:PMC3996531)

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.

• Item Type: Articles
• Additional Information: This work was supported by the Health Innovation Challenge Fund, the Wellcome Trust (grant reference 077012/Z/05/Z), and the Kay Kendall Leukaemia Fund. P.J.C. and S.M.J. are personally funded through Wellcome Trust Senior Clinical Research Fellowships. A.S. is funded by the H.L. Holmes Award from the National Research Council Canada and an EMBO fellowship. UAM is personally supported by a Cancer Research UK Clinician Scientist Fellowship. NB was supported by a starter grant from the Academy of Medical Sciences and from Lady Tata Memorial Trust. The breast cancer sequencing was supported by the BASIS project. The BASIS project is a European research project funded by the European Community’s Seventh Framework Programme (FP7/2010–2014) under the grant agreement number 242006. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We also acknowledge support for the sample banking and processing from UCL/UCLH NIHR Biomedical Centre, the Skeletal Cancer Action Trust (SCAT), especially Miss Dina Halai, and the Rosetrees Trust.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cooke, Dr Susie and Martin, Ms Sancha and Marshall, Mr John
• Authors: Cooke, S. L., Shlien, A., Marshall, J., Pipinikas, C. P., Martincorena, I., Tubio, J. M.C., Li, Y., Menzies, A., Mudie, L., Ramakrishna, M., Yates, L., Davies, H., Bolli, N., Bignell, G. R., Tarpey, P. S., Behjati, S., Nik-Zainal, S., Papaemmanuil, E., Teixeira, V. H., Raine, K., O’Meara, S., Dodoran, M. S., Teague, J. W., Butler, A. P., Iacobuzio-Donahue, C., Santarius, T., Grundy, R. G., Malkin, D., Greaves, M., Munshi, N., Flanagan, A. M., Bowtell, D., Martin, S., Larsimont, D., Reis-Filho, J. S., Boussioutas, A., Taylor, J., Hayes, N. D., Janes, S. M., Futreal, P. A., Stratton, M. R., McDermott, U., Campbell, P. J., Provenzano, E., van de Vijver, M., Richardson, A. L., Purdie, C., Pinder, S., Mac Grogan, G., Vincent-Salomon, A., Larsimont, D., Grabau, D., Sauer, T., Garred, Ø., Ehinger, A., Van den Eynden, G. G., van Deurzen, C.H.M., Salgado, R., Brock, J. E., Lakhani, S. R., Giri, D. D., Arnould, L., Jacquemier, J., Treilleux, I., Caldas, C., Chin, S.-F., Fatima, A., Thompson, A. M., Stenhouse, A., Foekens, J., Martens, J., Sieuwerts, A., Brinkman, A., Stunnenberg, H., Span, P. N., Sweep, F., Desmedt, C., Sotiriou, C., Thomas, G., Broeks, A., Langerod, A., Aparicio, S., Simpson, P. T., van ’t Veer, L., Erla Eyfjörd, J., Hilmarsdottir, H., Jonasson, J. G., Børresen-Dale, A.-L., Lee, M. T. M., Wong, B. H., Tan, B. K. T., and Hooijer, G. K.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright holders: © 2014 Macmillan Publishers Limited.
• First Published: First published in Nature Communications 5:3644
• Publisher Policy: Reproduced under a Creative Commons License