Mutational signatures of ionizing radiation in second malignancies

被引：201

作者：

Behjati, Sam ^{[1
,2
]}

Gundem, Gunes ^{[1
]}

Wedge, David C. ^{[1
,3
,4
]}

Roberts, Nicola D. ^{[1
]}

Tarpey, Patrick S. ^{[1
]}

Cooke, Susanna L. ^{[1
]}

Van Loo, Peter ^{[5
,6
]}

Alexandrov, Ludmil B. ^{[1
]}

Ramakrishna, Manasa ^{[1
]}

Davies, Helen ^{[1
]}

Nik-Zainal, Serena ^{[1
]}

Hardy, Claire ^{[1
]}

Latimer, Calli ^{[1
]}

Raine, Keiran M. ^{[1
]}

Stebbings, Lucy ^{[1
]}

Menzies, Andy ^{[1
]}

Jones, David ^{[1
]}

Shepherd, Rebecca ^{[1
]}

Butler, Adam P. ^{[1
]}

Teague, Jon W. ^{[1
]}

Jorgensen, Mette ^{[7
]}

Khatri, Bhavisha ^{[8
]}

Pillay, Nischalan ^{[7
,8
]}

Shlien, Adam ^{[1
,9
]}

Futreal, P. Andrew ^{[1
,10
]}

Badie, Christophe ^{[11
]}

McDermott, Ultan ^{[1
]}

Bova, G. Steven ^{[12
,13
]}

Richardson, Andrea L. ^{[14
,15
,17
]}

Flanagan, Adrienne M. ^{[7
,8
]}

Stratton, Michael R. ^{[1
]}

Campbell, Peter J. ^{[1
,16
]}

机构：

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

[2] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England

[3] Oxford Big Data Inst, Roosevelt Dr, Oxford OX3 7BN, England

[4] Wellcome Trust Ctr Human Genet, Oxford Ctr Canc Gene Res, Roosevelt Dr, Oxford OX3 7BN, England

[5] Francis Crick Inst, London WC2A 3LY, England

[6] Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium

[7] UCL, Inst Canc, Huntley St, London WC1E 6BT, England

[8] Royal Natl Orthopaed Hosp NHS Trust, Histopathol, Stanmore HA7 4LP, Middx, England

[9] Hosp Sick Children, Lab Med, Dept Paediat, Toronto, ON M5G 1X8, Canada

[10] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[11] Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Radiat Effects Dept, Canc Mech & Biomarkers Grp, Didcot OX11 0RQ, Oxon, England

[12] Univ Tampere, BioMediTech, Inst Biosci & Med Technol, FI-33520 Tampere, Finland

[13] Tampere Univ Hosp, Fimlab Labs, FI-33520 Tampere, Finland

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

[15] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[16] Univ Cambridge, Dept Haematol, Hills Rd, Cambridge CB2 2XY, England

[17] Johns Hopkins Med, Sibley Mem Hosp, Washington, DC 20016 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

英国惠康基金;

关键词：

GENOME-WIDE ANALYSIS; 21 BREAST CANCERS; INDUCED SARCOMAS; PROSTATE-CANCER; PAST EXPOSURE; RADIOTHERAPY; ANGIOSARCOMA; LYMPHOCYTES; MUTAGENESIS; INVERSIONS;

D O I：

10.1038/ncomms12605

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：

Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1-100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential.

引用

页数：8

共 44 条

[1] Angiosarcoma of the breast following surgery and radiotherapy for breast cancer [J].

Abbott, Rachel ;

Palmieri, Carlo .

NATURE CLINICAL PRACTICE ONCOLOGY, 2008, 5 (12) :727-736

[2] The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline [J].

Adewoye, Adeolu B. ;

Lindsay, Sarah J. ;

Dubrova, Yuri E. ;

Hurles, Matthew E. .

NATURE COMMUNICATIONS, 2015, 6

[3] Lymphocyte chromosomal aberration assay in radiation biodosimetry [J].

Agrawala, Paban K. ;

Adhikari, J. S. ;

Chaudhury, N. K. .

JOURNAL OF PHARMACY AND BIOALLIED SCIENCES, 2010, 2 (03) :197-201

[4] 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-+

[5] Mechanisms of therapy-related carcinogenesis [J].

Allan, JM ;

Lois, BT .

NATURE REVIEWS CANCER, 2005, 5 (12) :943-955

[6] Punctuated Evolution of Prostate Cancer Genomes [J].

Baca, Sylvan C. ;

Prandi, Davide ;

Lawrence, Michael S. ;

Mosquera, Juan Miguel ;

Romanel, Alessandro ;

Drier, Yotam ;

Park, Kyung ;

Kitabayashi, Naoki ;

MacDonald, Theresa Y. ;

Ghandi, Mahmoud ;

Van Allen, Eliezer ;

Kryukov, Gregory V. ;

Sboner, Andrea ;

Theurillat, Jean-Philippe ;

Soong, T. David ;

Nickerson, Elizabeth ;

Auclair, Daniel ;

Tewari, Ashutosh ;

Beltran, Himisha ;

Onofrio, Robert C. ;

Boysen, Gunther ;

Guiducci, Candace ;

Barbieri, Christopher E. ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Carter, Scott L. ;

Saksena, Gordon ;

Voet, Douglas ;

Ramos, Alex H. ;

Winckler, Wendy ;

Cipicchio, Michelle ;

Ardlie, Kristin ;

Kantoff, Philip W. ;

Berger, Michael F. ;

Gabriel, Stacey B. ;

Golub, Todd R. ;

Meyerson, Matthew ;

Lander, Eric S. ;

Elemento, Olivier ;

Getz, Gad ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Garraway, Levi A. .

CELL, 2013, 153 (03) :666-677

[7] Recurrent PTPRB and PLCG1 mutations in angiosarcoma [J].

Behjati, Sam ;

Tarpey, Patrick S. ;

Sheldon, Helen ;

Martincorena, Inigo ;

Van Loo, Peter ;

Gundem, Gunes ;

Wedge, David C. ;

Ramakrishna, Manasa ;

Cooke, Susanna L. ;

Pillay, Nischalan ;

Vollan, Hans Kristian M. ;

Papaemmanuil, Elli ;

Koss, Hans ;

Bunney, Tom D. ;

Hardy, Claire ;

Joseph, Olivia R. ;

Martin, Sancha ;

Mudie, Laura ;

Butler, Adam ;

Teague, Jon W. ;

Patil, Meena ;

Steers, Graham ;

Cao, Yu ;

Gumbs, Curtis ;

Ingram, Davis ;

Lazar, Alexander J. ;

Little, Latasha ;

Mahadeshwar, Harshad ;

Protopopov, Alexei ;

Al Sannaa, Ghadah A. ;

Seth, Sahil ;

Song, Xingzhi ;

Tang, Jiabin ;

Zhang, Jianhua ;

Ravi, Vinod ;

Torres, Keila E. ;

Khatri, Bhavisha ;

Halai, Dina ;

Roxanis, Ioannis ;

Baumhoer, Daniel ;

Tirabosco, Roberto ;

Amary, M. Fernanda ;

Boshoff, Chris ;

McDermott, Ultan ;

Katan, Matilda ;

Stratton, Michael R. ;

Futreal, P. Andrew ;

Flanagan, Adrienne M. ;

Harris, Adrian ;

Campbell, Peter J. .

NATURE GENETICS, 2014, 46 (04) :376-+

[8] Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana [J].

Belfield, Eric J. ;

Gan, Xiangchao ;

Mithani, Aziz ;

Brown, Carly ;

Jiang, Caifu ;

Franklin, Keara ;

Alvey, Elizabeth ;

Wibowo, Anjar ;

Jung, Marko ;

Bailey, Kit ;

Kalwani, Sharan ;

Ragoussis, Jiannis ;

Mott, Richard ;

Harberd, Nicholas P. .

GENOME RESEARCH, 2012, 22 (07) :1306-1315

[9] Heterogeneity of genomic evolution and mutational profiles in multiple myeloma [J].

Bolli, Niccolo ;

Avet-Loiseau, Herve ;

Wedge, David C. ;

Van Loo, Peter ;

Alexandrov, Ludmil B. ;

Martincorena, Inigo ;

Dawson, Kevin J. ;

Iorio, Francesco ;

Nik-Zainal, Serena ;

Bignell, Graham R. ;

Hinton, Jonathan W. ;

Li, Yilong ;

Tubio, Jose M. C. ;

McLaren, Stuart ;

Meara, Sarah O' ;

Butler, Adam P. ;

Teague, Jon W. ;

Mudie, Laura ;

Anderson, Elizabeth ;

Rashid, Naim ;

Tai, Yu-Tzu ;

Shammas, Masood A. ;

Sperling, Adam S. ;

Fulciniti, Mariateresa ;

Richardson, Paul G. ;

Parmigiani, Giovanni ;

Magrangeas, Florence ;

Minvielle, Stephane ;

Moreau, Philippe ;

Attal, Michel ;

Facon, Thierry ;

Futreal, P. Andrew ;

Anderson, Kenneth C. ;

Campbell, Peter J. ;

Munshi, Nikhil C. .

NATURE COMMUNICATIONS, 2014, 5

[10]

CAHAN WG, 1948, CANCER-AM CANCER SOC, V1, P3, DOI 10.1002/1097-0142(194805)1:1<3::AID-CNCR2820010103>3.0.CO

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