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 Oameara; 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; Peter J. Campbell; Elena Provenzano; Marc van de Vijver; Andrea L. Richardson; Colin Purdie; Sarah Pinder; Gaetan Mac Grogan; Anne Vincent-Salomon; Denis Larsimont; Dorthe Grabau; Torill Sauer; Øystein Garred; Anna Ehinger; Gert G. Van den Eynden; C. 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 Foekens; John Martens; Anieta Sieuwerts; Arjen Brinkman; Henk Stunnenberg; Paul N. Span; Fred Sweep; Christine Desmedt; Christos Sotiriou; Gilles Thomas; Annegein Broeks; Anita Langerod; Samuel Aparicio; Peter T. Simpson; Laura van ’t Veer; Jorunn Erla Eyfjord; Holmfridur Hilmarsdottir; Jon G. Jonasson; Anne Lise Børresen-Dale; Ming Ta Michael Lee; Bernice Huimin Wong; Benita Kiat Tee Tan; Gerrit K.J. Hooijer

doi:10.1038/ncomms4644

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 RaineSarah Oameara, 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, Peter J. Campbell, Elena Provenzano, Marc van de Vijver, Andrea L. Richardson, Colin Purdie, Sarah Pinder, Gaetan Mac Grogan, Anne Vincent-Salomon, Denis Larsimont, Dorthe Grabau, Torill Sauer, Øystein Garred, Anna Ehinger, Gert G. Van den Eynden, C. 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 Foekens, John Martens, Anieta Sieuwerts, Arjen Brinkman, Henk Stunnenberg, Paul N. Span, Fred Sweep, Christine Desmedt, Christos Sotiriou, Gilles Thomas, Annegein Broeks, Anita Langerod, Samuel Aparicio, Peter T. Simpson, Laura van ’t Veer, Jorunn Erla Eyfjord, Holmfridur Hilmarsdottir, Jon G. Jonasson, Anne Lise Børresen-Dale, Ming Ta Michael Lee, Bernice Huimin Wong, Benita Kiat Tee Tan, Gerrit K.J. Hooijer

Research output: Contribution to journal › Article › peer-review

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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%), 5a €2 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.

Original language	English (US)
Article number	3644
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4644
State	Published - Apr 9 2014
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms4644

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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., ... Hooijer, G. K. J. (2014). Processed pseudogenes acquired somatically during cancer development. Nature communications, 5, Article 3644. https://doi.org/10.1038/ncomms4644

Cooke, SL, Shlien, A, Marshall, J, Pipinikas, CP, Martincorena, I, Tubio, JMC, Li, Y, Menzies, A, Mudie, L, Ramakrishna, M, Yates, L, Davies, H, Bolli, N, Bignell, GR, Tarpey, PS, Behjati, S, Nik-Zainal, S, Papaemmanuil, E, Teixeira, VH, Raine, K, Oameara, S, Dodoran, MS, Teague, JW, Butler, AP, Iacobuzio-Donahue, C, Santarius, T, Grundy, RG, Malkin, D, Greaves, M, Munshi, N, Flanagan, AM, Bowtell, D, Martin, S, Larsimont, D, Reis-Filho, JS, Boussioutas, A, Taylor, JA, Hayes, ND, Janes, SM, Futreal, PA, Stratton, MR, McDermott, U, Campbell, PJ, Provenzano, E, van de Vijver, M, Richardson, AL, Purdie, C, Pinder, S, Grogan, GM, Vincent-Salomon, A, Larsimont, D, Grabau, D, Sauer, T, Garred, Ø, Ehinger, A, Van den Eynden, GG, van Deurzen, CHM, Salgado, R, Brock, JE, Lakhani, SR, Giri, DD, Arnould, L, Jacquemier, J, Treilleux, I, Caldas, C, Chin, SF, Fatima, A, Thompson, AM, Stenhouse, A, Foekens, J, Martens, J, Sieuwerts, A, Brinkman, A, Stunnenberg, H, Span, PN, Sweep, F, Desmedt, C, Sotiriou, C, Thomas, G, Broeks, A, Langerod, A, Aparicio, S, Simpson, PT, van ’t Veer, L, Eyfjord, JE, Hilmarsdottir, H, Jonasson, JG, Børresen-Dale, AL, Ta Michael Lee, M, Wong, BH, Tee Tan, BK & Hooijer, GKJ 2014, 'Processed pseudogenes acquired somatically during cancer development', Nature communications, vol. 5, 3644. https://doi.org/10.1038/ncomms4644

@article{3982168be0be4443a2cfdaed3ed857f7,

title = "Processed pseudogenes acquired somatically during cancer development",

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%), 5a €2 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.",

author = "Cooke, {Susanna L.} and Adam Shlien and John Marshall and Pipinikas, {Christodoulos P.} and Inigo Martincorena and Tubio, {Jose M.C.} and Yilong Li and Andrew Menzies and Laura Mudie and Manasa Ramakrishna and Lucy Yates and Helen Davies and Niccolo Bolli and Bignell, {Graham R.} and Tarpey, {Patrick S.} and Sam Behjati and Serena Nik-Zainal and Elli Papaemmanuil and Teixeira, {Vitor H.} and Keiran Raine and Sarah Oameara and Dodoran, {Maryam S.} and Teague, {Jon W.} and Butler, {Adam P.} and Christine Iacobuzio-Donahue and Thomas Santarius and Grundy, {Richard G.} and David Malkin and Mel Greaves and Nikhil Munshi and Flanagan, {Adrienne M.} and David Bowtell and Sancha Martin and Denis Larsimont and Reis-Filho, {Jorge S.} and Alex Boussioutas and Taylor, {Jack A.} and Hayes, {Neil D.} and Janes, {Sam M.} and Futreal, {P. Andrew} and Stratton, {Michael R.} and Ultan McDermott and Campbell, {Peter J.} and Elena Provenzano and {van de Vijver}, Marc and Richardson, {Andrea L.} and Colin Purdie and Sarah Pinder and Grogan, {Gaetan Mac} and Anne Vincent-Salomon and Denis Larsimont and Dorthe Grabau and Torill Sauer and {\O}ystein Garred and Anna Ehinger and {Van den Eynden}, {Gert G.} and {van Deurzen}, {C. H.M.} and Roberto Salgado and Brock, {Jane E.} and Lakhani, {Sunil R.} and Giri, {Dilip D.} and Laurent Arnould and Jocelyne Jacquemier and Isabelle Treilleux and Carlos Caldas and Chin, {Suet Feung} and Aquila Fatima and Thompson, {Alastair M.} and Alasdair Stenhouse and John Foekens and John Martens and Anieta Sieuwerts and Arjen Brinkman and Henk Stunnenberg and Span, {Paul N.} and Fred Sweep and Christine Desmedt and Christos Sotiriou and Gilles Thomas and Annegein Broeks and Anita Langerod and Samuel Aparicio and Simpson, {Peter T.} and {van {\textquoteright}t Veer}, Laura and Eyfjord, {Jorunn Erla} and Holmfridur Hilmarsdottir and Jonasson, {Jon G.} and B{\o}rresen-Dale, {Anne Lise} and {Ta Michael Lee}, Ming and Wong, {Bernice Huimin} and {Tee Tan}, {Benita Kiat} and Hooijer, {Gerrit K.J.}",

note = "Funding 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{\textquoteright}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.",

year = "2014",

month = apr,

day = "9",

doi = "10.1038/ncomms4644",

language = "English (US)",

volume = "5",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Processed pseudogenes acquired somatically during cancer development

AU - Cooke, Susanna L.

AU - Shlien, Adam

AU - Marshall, John

AU - Pipinikas, Christodoulos P.

AU - Martincorena, Inigo

AU - Tubio, Jose M.C.

AU - Li, Yilong

AU - Menzies, Andrew

AU - Mudie, Laura

AU - Ramakrishna, Manasa

AU - Yates, Lucy

AU - Davies, Helen

AU - Bolli, Niccolo

AU - Bignell, Graham R.

AU - Tarpey, Patrick S.

AU - Behjati, Sam

AU - Nik-Zainal, Serena

AU - Papaemmanuil, Elli

AU - Teixeira, Vitor H.

AU - Raine, Keiran

AU - Oameara, Sarah

AU - Dodoran, Maryam S.

AU - Teague, Jon W.

AU - Butler, Adam P.

AU - Iacobuzio-Donahue, Christine

AU - Santarius, Thomas

AU - Grundy, Richard G.

AU - Malkin, David

AU - Greaves, Mel

AU - Munshi, Nikhil

AU - Flanagan, Adrienne M.

AU - Bowtell, David

AU - Martin, Sancha

AU - Larsimont, Denis

AU - Reis-Filho, Jorge S.

AU - Boussioutas, Alex

AU - Taylor, Jack A.

AU - Hayes, Neil D.

AU - Janes, Sam M.

AU - Futreal, P. Andrew

AU - Stratton, Michael R.

AU - McDermott, Ultan

AU - Campbell, Peter J.

AU - Provenzano, Elena

AU - van de Vijver, Marc

AU - Richardson, Andrea L.

AU - Purdie, Colin

AU - Pinder, Sarah

AU - Grogan, Gaetan Mac

AU - Vincent-Salomon, Anne

AU - Larsimont, Denis

AU - Grabau, Dorthe

AU - Sauer, Torill

AU - Garred, Øystein

AU - Ehinger, Anna

AU - Van den Eynden, Gert G.

AU - van Deurzen, C. H.M.

AU - Salgado, Roberto

AU - Brock, Jane E.

AU - Lakhani, Sunil R.

AU - Giri, Dilip D.

AU - Arnould, Laurent

AU - Jacquemier, Jocelyne

AU - Treilleux, Isabelle

AU - Caldas, Carlos

AU - Chin, Suet Feung

AU - Fatima, Aquila

AU - Thompson, Alastair M.

AU - Stenhouse, Alasdair

AU - Foekens, John

AU - Martens, John

AU - Sieuwerts, Anieta

AU - Brinkman, Arjen

AU - Stunnenberg, Henk

AU - Span, Paul N.

AU - Sweep, Fred

AU - Desmedt, Christine

AU - Sotiriou, Christos

AU - Thomas, Gilles

AU - Broeks, Annegein

AU - Langerod, Anita

AU - Aparicio, Samuel

AU - Simpson, Peter T.

AU - van ’t Veer, Laura

AU - Eyfjord, Jorunn Erla

AU - Hilmarsdottir, Holmfridur

AU - Jonasson, Jon G.

AU - Børresen-Dale, Anne Lise

AU - Ta Michael Lee, Ming

AU - Wong, Bernice Huimin

AU - Tee Tan, Benita Kiat

AU - Hooijer, Gerrit K.J.

N1 - Funding 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.

PY - 2014/4/9

Y1 - 2014/4/9

N2 - 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%), 5a €2 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.

AB - 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%), 5a €2 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84898458784&partnerID=8YFLogxK

U2 - 10.1038/ncomms4644

DO - 10.1038/ncomms4644

M3 - Article

C2 - 24714652

AN - SCOPUS:84898458784

SN - 2041-1723

VL - 5

JO - Nature communications

JF - Nature communications

M1 - 3644

ER -

Processed pseudogenes acquired somatically during cancer development

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