deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution

被引：848

作者：

Rosenthal, Rachel ^{[1
,2
,4
]}

McGranahan, Nicholas ^{[1
,2
,3
]}

Herrero, Javier ^{[4
]}

Taylor, Barry S. ^{[5
,6
,7
]}

Swanton, Charles ^{[1
,2
]}

机构：

[1] UCL, Inst Canc, CRUK Lung Canc Ctr Excellence, Paul OGorman Bldg,Huntley St, London WC1E 6DD, England

[2] Francis Crick Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England

[3] UCL, Ctr Math & Phys Life Sci & Expt Biol CoMPLEX, London WC1E 6BT, England

[4] UCL, Inst Canc, Bill Lyons Informat Ctr, Paul OGorman Bldg,Huntley St, London WC1E 6DD, England

[5] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[7] Mem Sloan Kettering Canc Ctr, Ctr Mol Oncol, 1275 York Ave, New York, NY 10021 USA

来源：

GENOME BIOLOGY | 2016年 / 17卷

基金：

欧洲研究理事会;

关键词：

Mutational signatures; Esophageal carcinoma; APOBEC; Single samples; SIGNATURES;

D O I：

10.1186/s13059-016-0893-4

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Background: Analysis of somatic mutations provides insight into the mutational processes that have shaped the cancer genome, but such analysis currently requires large cohorts. We develop deconstructSigs, which allows the identification of mutational signatures within a single tumor sample. Results: Application of deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct and dynamic mutational processes molding the cancer genome in esophageal adenocarcinoma compared to squamous cell carcinomas. Conclusions: deconstructSigs confers the ability to define mutational processes driven by environmental exposures, DNA repair abnormalities, and mutagenic processes in individual tumors with implications for precision cancer medicine.

引用

页数：11

共 10 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]

Deciphering Signatures of Mutational Processes Operative in Human Cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Campbell, Peter J. ;

Stratton, Michael R. .

CELL REPORTS, 2013, 3 (01) :246-259

[3]

Boland CR, 2010, GASTROENTEROLOGY, V138, P2073, DOI [10.1053/j.gastro.2010.04.024, 10.1053/j.gastro.2009.12.064]

[4]

Spatial and temporal diversity in genomic instability processes defines lung cancer evolution [J].

de Bruin, Elza C. ;

McGranahan, Nicholas ;

Mitter, Richard ;

Salm, Max ;

Wedge, David C. ;

Yates, Lucy ;

Jamal-Hanjani, Mariam ;

Shafi, Seema ;

Murugaesu, Nirupa ;

Rowan, Andrew J. ;

Groenroos, Eva ;

Muhammad, Madiha A. ;

Horswell, Stuart ;

Gerlinger, Marco ;

Varela, Ignacio ;

Jones, David ;

Marshall, John ;

Voet, Thierry ;

Van Loo, Peter ;

Rassl, Doris M. ;

Rintoul, Robert C. ;

Janes, Sam M. ;

Lee, Siow-Ming ;

Forster, Martin ;

Ahmad, Tanya ;

Lawrence, David ;

Falzon, Mary ;

Capitanio, Arrigo ;

Harkins, Timothy T. ;

Lee, Clarence C. ;

Tom, Warren ;

Teefe, Enock ;

Chen, Shann-Ching ;

Begum, Sharmin ;

Rabinowitz, Adam ;

Phillimore, Benjamin ;

Spencer-Dene, Bradley ;

Stamp, Gordon ;

Szallasi, Zoltan ;

Matthews, Nik ;

Stewart, Aengus ;

Campbell, Peter ;

Swanton, Charles .

SCIENCE, 2014, 346 (6206) :251-256

[5]

Mechanisms underlying mutational signatures in human cancers [J].

Helleday, Thomas ;

Eshtad, Saeed ;

Nik-Zainal, Serena .

NATURE REVIEWS GENETICS, 2014, 15 (09) :585-598

[6]

Clonal status of actionable driver events and the timing of mutational processes in cancer evolution [J].

McGranahan, Nicholas ;

Favero, Francesco ;

de Bruin, Elza C. ;

Birkbak, Nicolai Juul ;

Szallasi, Zoltan ;

Swanton, Charles .

SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (283)

[7]

Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy [J].

Murugaesu, Nirupa ;

Wilson, Gareth A. ;

Birkbak, Nicolai J. ;

Watkins, Thomas B. K. ;

McGranahan, Nicholas ;

Kumar, Sacheen ;

Abbassi-Ghadi, Nima ;

Salm, Max ;

Mitter, Richard ;

Horswell, Stuart ;

Rowan, Andrew ;

Phillimore, Benjamin ;

Biggs, Jennifer ;

Begum, Sharmin ;

Matthews, Nik ;

Hochhauser, Daniel ;

Hanna, George B. ;

Swanton, Charles .

CANCER DISCOVERY, 2015, 5 (08) :821-831

[8]

Pages H., BSGENOME INFRASTRUCT

[9]

Environmental exposures and mutational patterns of cancer genomes [J].

Pfeifer, Gerd P. .

GENOME MEDICINE, 2010, 2

[10]

Wickham H, 2007, J STAT SOFTW, V21, P1

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