Processed pseudogenes acquired somatically during cancer development

被引：79

作者：

Cooke, Susanna L. ^{[1
]}

Shlien, Adam ^{[1
]}

Marshall, John ^{[1
]}

Pipinikas, Christodoulos P. ^{[2
]}

Martincorena, Inigo ^{[1
]}

Tubio, Jose M. C. ^{[1
]}

Li, Yilong ^{[1
]}

Menzies, Andrew ^{[1
]}

Mudie, Laura ^{[1
]}

Ramakrishna, Manasa ^{[1
]}

Yates, Lucy ^{[1
]}

Davies, Helen ^{[1
]}

Bolli, Niccolo ^{[1
,3
]}

Bignell, Graham R. ^{[1
]}

Tarpey, Patrick S. ^{[1
]}

Behjati, Sam ^{[1
,3
]}

Nik-Zainal, Serena ^{[1
]}

Papaemmanuil, Elli ^{[1
]}

Teixeira, Vitor H. ^{[2
]}

Raine, Keiran ^{[1
]}

O'Meara, Sarah ^{[1
]}

Dodoran, Maryam S. ^{[1
]}

Teague, Jon W. ^{[1
]}

Butler, Adam P. ^{[1
]}

Iacobuzio-Donahue, Christine ^{[4
,5
]}

Santarius, Thomas ^{[6
]}

Grundy, Richard G. ^{[7
]}

Malkin, David ^{[8
]}

Greaves, Mel ^{[9
]}

Munshi, Nikhil ^{[10
]}

Flanagan, Adrienne M. ^{[11
]}

Bowtell, David ^{[12
]}

Martin, Sancha ^{[1
]}

Larsimont, Denis ^{[13
]}

Reis-Filho, Jorge S. ^{[14
]}

Boussioutas, Alex ^{[15
]}

Taylor, Jack A. ^{[16
]}

Hayes, D. Neil ^{[17
]}

Janes, Sam M. ^{[2
]}

Futreal, P. Andrew ^{[1
]}

Stratton, Michael R. ^{[1
]}

McDermott, Ultan ^{[1
,6
]}

Campbell, Peter J. ^{[6
,14
]}

机构：

[1] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England

[2] UCL, Lungs Living Res Ctr, Rayne Inst, London WC1E 6JF, England

[3] Univ Cambridge, Cambridge CB2 0XY, England

[4] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

[5] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA

[6] Addenbrookes NHS Fdn Trust, Cambridge CB2 0QQ, England

[7] Univ Nottingham, Childrens Brain Tumour Res Ctr, Nottingham NG7 2UH, England

[8] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada

[9] Inst Canc Res, Sutton SM2 5NG, Surrey, England

[10] Dana Farber Canc Inst, Boston, MA 02215 USA

[11] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England

[12] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia

[13] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium

[14] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[15] Univ Melbourne, Royal Melbourne Hosp, Dept Gastroenterol, Parkville, Vic 3050, Australia

[16] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27713 USA

[17] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

英国惠康基金;

关键词：

L1; RETROTRANSPOSITION; MUTATIONAL PROCESSES; GENE-EXPRESSION; REARRANGEMENT; LANDSCAPE; ACTIVATION; REVEALS; GENOMES; LINE-1;

D O I：

10.1038/ncomms4644

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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%), 50 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.

引用

页数：9

共 42 条

[1] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[2] Retrocopy contributions to the evolution of the human genome [J].

Baertsch, Robert ;

Diekhans, Mark ;

Kent, W. James ;

Haussler, David ;

Brosius, Juergen .

BMC GENOMICS, 2008, 9 (1)

[3] Somatic retrotransposition alters the genetic landscape of the human brain [J].

Baillie, J. Kenneth ;

Barnett, Mark W. ;

Upton, Kyle R. ;

Gerhardt, Daniel J. ;

Richmond, Todd A. ;

De Sapio, Fioravante ;

Brennan, Paul ;

Rizzu, Patrizia ;

Smith, Sarah ;

Fell, Mark ;

Talbot, Richard T. ;

Gustincich, Stefano ;

Freeman, Thomas C. ;

Mattick, John S. ;

Hume, David A. ;

Heutink, Peter ;

Carninci, Piero ;

Jeddeloh, Jeffrey A. ;

Faulkner, Geoffrey J. .

NATURE, 2011, 479 (7374) :534-537

[4] The patterns and dynamics of genomic instability in metastatic pancreatic cancer [J].

Campbell, Peter J. ;

Yachida, Shinichi ;

Mudie, Laura J. ;

Stephens, Philip J. ;

Pleasance, Erin D. ;

Stebbings, Lucy A. ;

Morsberger, Laura A. ;

Latimer, Calli ;

McLaren, Stuart ;

Lin, Meng-Lay ;

McBride, David J. ;

Varela, Ignacio ;

Nik-Zainal, Serena A. ;

Leroy, Catherine ;

Jia, Mingming ;

Menzies, Andrew ;

Butler, Adam P. ;

Teague, Jon W. ;

Griffin, Constance A. ;

Burton, John ;

Swerdlow, Harold ;

Quail, Michael A. ;

Stratton, Michael R. ;

Iacobuzio-Donahue, Christine ;

Futreal, P. Andrew .

NATURE, 2010, 467 (7319) :1109-1113

[5] Human L1 element target-primed reverse transcription in vitro [J].

Cost, GJ ;

Feng, QH ;

Jacquier, A ;

Boeke, JD .

EMBO JOURNAL, 2002, 21 (21) :5899-5910

[6] L1 retrotransposition in human neural progenitor cells [J].

Coufal, Nicole G. ;

Garcia-Perez, Jose L. ;

Peng, Grace E. ;

Yeo, Gene W. ;

Mu, Yangling ;

Lovci, Michael T. ;

Morell, Maria ;

O'Shea, K. Sue ;

Moran, John V. ;

Gage, Fred H. .

NATURE, 2009, 460 (7259) :1127-1131

[7] High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations [J].

Edelmann, Jennifer ;

Holzmann, Karlheinz ;

Miller, Florian ;

Winkler, Dirk ;

Buehler, Andreas ;

Zenz, Thorsten ;

Bullinger, Lars ;

Kuehn, Michael W. M. ;

Gerhardinger, Andreas ;

Bloehdorn, Johannes ;

Radtke, Ina ;

Su, Xiaoping ;

Ma, Jing ;

Pounds, Stanley ;

Hallek, Michael ;

Lichter, Peter ;

Korbel, Jan ;

Busch, Raymonde ;

Mertens, Daniel ;

Downing, James R. ;

Stilgenbauer, Stephan ;

Doehner, Hartmut .

BLOOD, 2012, 120 (24) :4783-4794

[8] Human LINE retrotransposons generate processed pseudogenes [J].

Esnault, C ;

Maestre, J ;

Heidmann, T .

NATURE GENETICS, 2000, 24 (04) :363-367

[9] Single-Neuron Sequencing Analysis of L1 Retrotransposition and Somatic Mutation in the Human Brain [J].

Evrony, Gilad D. ;

Cai, Xuyu ;

Lee, Eunjung ;

Hills, L. Benjamin ;

Elhosary, Princess C. ;

Lehmann, Hillel S. ;

Parker, J. J. ;

Atabay, Kutay D. ;

Gilmore, Edward C. ;

Poduri, Annapurna ;

Park, Peter J. ;

Walsh, Christopher A. .

CELL, 2012, 151 (03) :483-496

[10] 3'UTR-Mediated Gene Silencing of the Mixed Lineage Leukemia (MLL) Gene [J].

Gomez-Benito, Maria ;

Loayza-Puch, Fabricio ;

Vrielink, Joachim Oude ;

Odero, Maria D. ;

Agami, Reuven .

PLOS ONE, 2011, 6 (10)

← 1 2 3 4 5 →