Mutational signatures associated with tobacco smoking in human cancer
Ludmil B. Alexandrov,Ludmil B. Alexandrov,Young Seok Ju,Kerstin Haase,Peter Van Loo,Peter Van Loo,Inigo Martincorena,Serena Nik-Zainal,Serena Nik-Zainal,Yasushi Totoki,Akihiro Fujimoto,Hidewaki Nakagawa,Tatsuhiro Shibata,Peter J. Campbell,Peter J. Campbell,Paolo Vineis,David H. Phillips,Michael R. Stratton +17 more
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TLDR
The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.Abstract:
Tobacco smoking increases the risk of at least 17 classes of human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.read more
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Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
Zachary R. Chalmers,Caitlin F. Connelly,David Fabrizio,Siraj M. Ali,Riley Ennis,Alexa B. Schrock,Brittany Campbell,Adam Shlien,Juliann Chmielecki,Franklin W. Huang,Yuting He,James Sun,Uri Tabori,Mark Kennedy,Daniel S. Lieber,Steven Roels,Jared White,G. Otto,Jeffrey S. Ross,Levi A. Garraway,Levi A. Garraway,Vincent A. Miller,Phillip J. Stephens,Garrett M. Frampton +23 more
TL;DR: Measurements of TMB from comprehensive genomic profiling are strongly reflective of measurements from whole exome sequencing and model that below 0.5 Mb the variance in measurement increases significantly, demonstrating that many disease types have a substantial portion of patients with high TMB who might benefit from immunotherapy.
Journal ArticleDOI
Putting p53 in Context
TL;DR: TP53 is the most frequently mutated gene in human cancer and must be interpreted to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might it restore its tumor-suppressive activities in cancer.
Journal ArticleDOI
Small-cell lung cancer: what we know, what we need to know and the path forward
TL;DR: Over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts, which have led to the discovery of new potential therapeutic vulnerabilities for SCLc and therefore to new clinical trials.
Journal ArticleDOI
A compendium of mutational cancer driver genes.
Francisco Martínez-Jiménez,Ferran Muiños,Inés Sentís,Jordi Deu-Pons,Iker Reyes-Salazar,Claudia Arnedo-Pac,Loris Mularoni,Oriol Pich,Jose Bonet,Hanna Kranas,Abel Gonzalez-Perez,Nuria Lopez-Bigas,Nuria Lopez-Bigas +12 more
TL;DR: This Review provides a brief historical perspective of the role of cancer genes before presenting the Integrative OncoGenomics (IntOGen) platform, a bioinformatics method of mutational driver identification, which is beginning to reveal the compendium of driver genes across many tumour types as well as alluding to their tumorigenic mechanisms.
Journal ArticleDOI
MutationalPatterns: comprehensive genome-wide analysis of mutational processes
TL;DR: MutationalPatterns, an R/Bioconductor package that allows researchers to characterize a broad range of patterns in base substitution catalogues to dissect the underlying molecular mechanisms, offers an efficient method to quantify the contribution of known mutational signatures within single samples.
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TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.
Journal ArticleDOI
Signatures of mutational processes in human cancer
Ludmil B. Alexandrov,Serena Nik-Zainal,Serena Nik-Zainal,David C. Wedge,Samuel Aparicio,Sam Behjati,Sam Behjati,Andrew V. Biankin,Graham R. Bignell,Niccolo Bolli,Niccolo Bolli,Åke Borg,Anne Lise Børresen-Dale,Anne Lise Børresen-Dale,Sandrine Boyault,Birgit Burkhardt,Adam Butler,Carlos Caldas,Helen Davies,Christine Desmedt,Roland Eils,Jorunn E. Eyfjord,John A. Foekens,Mel Greaves,Fumie Hosoda,Barbara Hutter,Tomislav Ilicic,Sandrine Imbeaud,Sandrine Imbeaud,Marcin Imielinsk,Natalie Jäger,David T. W. Jones,David T. Jones,Stian Knappskog,Stian Knappskog,Marcel Kool,Sunil R. Lakhani,Carlos López-Otín,Sancha Martin,Nikhil C. Munshi,Nikhil C. Munshi,Hiromi Nakamura,Paul A. Northcott,Marina Pajic,Elli Papaemmanuil,Angelo Paradiso,John V. Pearson,Xose S. Puente,Keiran Raine,Manasa Ramakrishna,Andrea L. Richardson,Andrea L. Richardson,Julia Richter,Philip Rosenstiel,Matthias Schlesner,Ton N. Schumacher,Paul N. Span,Jon W. Teague,Yasushi Totoki,Andrew Tutt,Rafael Valdés-Mas,Marit M. van Buuren,Laura van ’t Veer,Anne Vincent-Salomon,Nicola Waddell,Lucy R. Yates,Icgc PedBrain,Jessica Zucman-Rossi,Jessica Zucman-Rossi,P. Andrew Futreal,Ultan McDermott,Peter Lichter,Matthew Meyerson,Matthew Meyerson,Sean M. Grimmond,Reiner Siebert,Elias Campo,Tatsuhiro Shibata,Stefan M. Pfister,Stefan M. Pfister,Peter J. Campbell,Peter J. Campbell,Peter J. Campbell,Michael R. Stratton,Michael R. Stratton +84 more
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Journal ArticleDOI
An integrated map of genetic variation from 1,092 human genomes
Gonçalo R. Abecasis,Adam Auton,Lisa D. Brooks,Mark A. DePristo,Richard Durbin,Robert E. Handsaker,Robert E. Handsaker,Hyun Min Kang,Gabor T. Marth,Gil McVean +9 more
TL;DR: It is shown that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites.
Journal ArticleDOI
Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010
Theo Vos,Abraham D. Flaxman,Mohsen Naghavi,Rafael Lozano,Catherine Michaud,Majid Ezzati,Kenji Shibuya,Joshua A. Salomon,Safa Abdalla,Victor Aboyans,Jerry Abraham,Ilana N. Ackerman,Rakesh Aggarwal,Stephanie Y. Ahn,Mohammed K. Ali,Mohammad A. AlMazroa,Miriam Alvarado,H. Ross Anderson,Laurie M. Anderson,Kathryn G. Andrews,Charles Atkinson,Larry M. Baddour,Adil N. Bahalim,Suzanne Barker-Collo,Lope H Barrero,David Bartels,María-Gloria Basáñez,Amanda J Baxter,Michelle L. Bell,Emelia J. Benjamin,Derrick A Bennett,Eduardo Bernabé,Kavi Bhalla,Bishal Bhandari,Boris Bikbov,Aref A. Bin Abdulhak,Gretchen L. Birbeck,James A. Black,Hannah Blencowe,Jed D. Blore,Fiona M. Blyth,Ian Bolliger,Audrey Bonaventure,Soufiane Boufous,Rupert R A Bourne,Michel Boussinesq,Tasanee Braithwaite,Carol Brayne,Lisa Bridgett,Simon Brooker,Peter Brooks,Traolach S. Brugha,Claire Bryan-Hancock,Chiara Bucello,Rachelle Buchbinder,Geoffrey Buckle,Christine M. Budke,Michael Burch,Peter Burney,Roy Burstein,Bianca Calabria,Benjamin L. Campbell,Charles E. Canter,Hélène Carabin,Jonathan R. Carapetis,Loreto Carmona,Claudia Cella,Fiona J Charlson,Honglei Chen,Andrew T. A. Cheng,David Chou,Sumeet S. Chugh,Luc E. Coffeng,Steven D. Colan,Samantha M. Colquhoun,K. Ellicott Colson,John R. Condon,Myles Connor,Myles Connor,Myles Connor,Leslie T. Cooper,Matthew A. Corriere,Monica Cortinovis,Karen Courville De Vaccaro,William G. Couser,Benjamin C Cowie,Michael H. Criqui,Marita Cross,Kaustubh Dabhadkar,Manu Dahiya,Nabila Dahodwala,James Damsere-Derry,Goodarz Danaei,Adrian Davis,Diego De Leo,Louisa Degenhardt,Robert P. Dellavalle,Allyne Delossantos,Julie O. Denenberg,Sarah Derrett,Don C. Des Jarlais,Samath D Dharmaratne,Samath D Dharmaratne,Mukesh Dherani,Cesar Diaz-Torne,Helen Dolk,E. Ray Dorsey,Tim Driscoll,Herbert C. Duber,Beth E. Ebel,Karen Edmond,Alexis Elbaz,S. Ali,Holly E. Erskine,Patricia J. Erwin,Patricia Espindola,Stalin E. Ewoigbokhan,Farshad Farzadfar,Valery L. Feigin,David T. Felson,Alize J. Ferrari,Cleusa P. Ferri,Eric M. Fèvre,Mariel M. Finucane,Seth Flaxman,Louise Flood,Kyle J Foreman,Mohammad H. Forouzanfar,F.G.R. Fowkes,Richard C. Franklin,Richard C. Franklin,Marlene Fransen,Michael Freeman,Belinda J. Gabbe,Sherine E. Gabriel,Emmanuela Gakidou,Hammad A. Ganatra,Bianca Garcia,Flavio Gaspari,Richard F. Gillum,Gerhard Gmel,Richard A. Gosselin,Rebecca Grainger,Justina Groeger,Francis Guillemin,David Gunnell,R Gupta,Juanita A. Haagsma,Holly Hagan,Yara A. Halasa,Wayne Hall,Diana Haring,Josep Maria Haro,James Harrison,Rasmus Havmoeller,Roderick J. Hay,Hideki Higashi,Christopher Hill,Bruno Hoen,Howard J. Hoffman,Peter J. Hotez,Damian G Hoy,John J Huang,Sydney E. Ibeanusi,Kathryn H. Jacobsen,Spencer L. James,Deborah Jarvis,Rashmi Jasrasaria,Sudha Jayaraman,Nicole E. Johns,Jost B. Jonas,Ganesan Karthikeyan,Nicholas J Kassebaum,Norito Kawakami,Andre Keren,Jon Paul Khoo,Charles H. King,Lisa M. Knowlton,Olive Kobusingye,Olive Kobusingye,Adofo Koranteng,Rita Krishnamurthi,Ratilal Lalloo,Laura L Laslett,Tim Lathlean,Janet L Leasher,Yong Yi Lee,James Leigh,Stephen S Lim,Elizabeth S Limb,John K Lin,Michael S Lipnick,Steven E. Lipshultz,Wei Liu,Maria Loane,Summer Lockett Ohno,Ronan A Lyons,Jixiang Ma,Jacqueline Mabweijano,Michael F. MacIntyre,Reza Malekzadeh,Leslie Mallinger,Sivabalan Manivannan,Wagner Marcenes,Lyn March,David J. Margolis,Guy B. Marks,Robin Marks,Akira Matsumori,Richard Matzopoulos,Richard Matzopoulos,Bongani M. Mayosi,John H. McAnulty,Mary M. McDermott,Neil McGill,John J. McGrath,María Elena Medina-Mora,Michele Meltzer,Ziad A. Memish,George A. Mensah,Tony R. Merriman,Ana-Claire Meyer,Valeria Miglioli,Matthew J. Miller,Ted R. Miller,Philip B. Mitchell,Ana Olga Mocumbi,Terrie E. Moffitt,Ali A. Mokdad,Lorenzo Monasta,Marcella Montico,Maziar Moradi-Lakeh,Andrew E. Moran,Lidia Morawska,Rintaro Mori,Michele E. Murdoch,Michael K Mwaniki,Kovin Naidoo,M. Nathan Nair,Luigi Naldi,K.M. Venkat Narayan,Paul K. Nelson,Robert G. Nelson,Michael C. Nevitt,Charles R. Newton,Sandra Nolte,Paul Norman,Rosana E. Norman,Martin O'Donnell,Simon J. O’Hanlon,Casey Olives,Saad B. Omer,Katrina F Ortblad,Richard H. Osborne,Doruk Ozgediz,Andrew Page,Bishnu Pahari,Jeyaraj D Pandian,Andrea Panozo Rivero,Scott B. Patten,Neil Pearce,Rogelio Perez Padilla,Fernando Perez-Ruiz,Norberto Perico,Konrad Pesudovs,David Phillips,Michael R. Phillips,Kelsey Pierce,Sébastien D. S. Pion,Guilherme V. Polanczyk,Suzanne Polinder,C. Arden Pope,Svetlana Popova,Esteban Porrini,Farshad Pourmalek,Martin Prince,Rachel L. Pullan,Kapa D. Ramaiah,Dharani Ranganathan,Homie Razavi,Mathilda Regan,Jürgen Rehm,David B. Rein,G. Remuzzi,Kathryn Richardson,Frederick P. Rivara,Thomas Roberts,Carolyn Robinson,Felipe Rodriguez De Leòn,Luca Ronfani,Robin Room,Lisa C. Rosenfeld,Lesley Rushton,Ralph L. Sacco,Sukanta Saha,Uchechukwu Sampson,Lidia Sanchez-Riera,Ella Sanman,David C. Schwebel,James Scott,Maria Segui-Gomez,Saeid Shahraz,Donald S. Shepard,Hwashin Shin,Rupak Shivakoti,Donald H. Silberberg,David Singh,Gitanjali M Singh,Jasvinder A. Singh,Jessica Singleton,David A. Sleet,Karen Sliwa,Emma Smith,Jennifer L. Smith,Nicolas J. C. Stapelberg,Andrew C Steer,Timothy J. Steiner,Wilma A. Stolk,Lars Jacob Stovner,Christopher R. Sudfeld,Sana Syed,Giorgio Tamburlini,Mohammad Tavakkoli,Hugh R. Taylor,Jennifer A. Taylor,William J. Taylor,Bernadette Thomas,W. Murray Thomson,George D. Thurston,Imad M. Tleyjeh,Marcello Tonelli,Jeffrey A. Towbin,Thomas Truelsen,Miltiadis K. Tsilimbaris,Clotilde Ubeda,Eduardo A. Undurraga,Marieke J. van der Werf,Jim van Os,Monica S. Vavilala,Narayanaswamy Venketasubramanian,Mengru Wang,Wenzhi Wang,Kerrianne Watt,David Weatherall,Martin A. Weinstock,Robert G. Weintraub,Marc G. Weisskopf,Myrna M. Weissman,Richard A. White,Harvey Whiteford,Steven T. Wiersma,James D. Wilkinson,Hywel C Williams,Sean R.M. Williams,Emma Witt,Frederick Wolfe,Anthony D. Woolf,Sarah Wulf,Pon Hsiu Yeh,Anita K. M. Zaidi,Zhi Jie Zheng,David Zonies,Alan D. Lopez,Christopher J L Murray +363 more
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
Journal ArticleDOI
dbSNP: the NCBI database of genetic variation
Stephen T. Sherry,Minghong Ward,Michael Kholodov,Jonathan Baker,Lon Phan,Elizabeth M. Smigielski,Karl Sirotkin +6 more
TL;DR: The dbSNP database is a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, and is integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data.
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Park,Katherine A. Hoadley,J. Todd Auman,Shaowu Meng,Yan Shi,Elizabeth Buda,Scot Waring,Umadevi Veluvolu,Donghui Tan,Piotr A. Mieczkowski,Corbin D. Jones,Janae V. Simons,Matthew G. Soloway,Tom Bodenheimer,Stuart R. Jefferys,Jeffrey Roach,Alan P. Hoyle,Junyuan Wu,Saianand Balu,Darshan Singh,Jan F. Prins,James Stephen Marron,Joel S. Parker,Charles M. Perou,Jinze Liu,Dennis T. Maglinte,Philip H. Lai,Moiz S. Bootwalla,David Van Den Berg,Timothy J. Triche,Juok Cho,Daniel DiCara,David I. Heiman,Pei Lin,William Mallard,Douglas Voet,Hailei Zhang,Lihua Zou,Michael S. Noble,Nils Gehlenborg,Helga Thorvaldsdottir,Marc Danie Nazaire,James T. Robinson,B. Arman Aksoy,Giovanni Ciriello,Barry S. Taylor,Gideon Dresdner,Jianjiong Gao,Benjamin Gross,Venkatraman E. Seshan,Boris Reva,S. Onur Sumer,Nils Weinhold,Chris Sander,Sam Ng,Jingchun Zhu,Christopher C. Benz,Christina Yau,David Haussler,Paul T. Spellman,Patrick K. Kimes,Bradley M. Broom,Jing Wang,Yiling Lu,Patrick Kwok Shing Ng,Lixia Diao,Wenbin Liu,Christopher I. Amos,Rehan Akbani,Gordon B. Mills,Erin Curley,Joseph Paulauskis,Kevin Lau,Scott Morris,Troy Shelton,David Mallery,Johanna Gardner,Robert Penny,Charles Saller,Katherine Tarvin,William G. Richards,Robert J. Cerfolio,Ayesha S. Bryant,Daniel P. Raymond,Nathan A. Pennell,Carol Farver,Christine Czerwinski,Lori Huelsenbeck-Dill,Mary Iacocca,Nicholas J. Petrelli,Brenda Rabeno,Jennifer Brown,Thomas L. Bauer,Cureline Oleg Dolzhanskiy,Olga Potapova,D L Rotin,Olga Voronina,Elena Nemirovich-Danchenko,Konstantin V. Fedosenko,Anthony A. Gal,Madhusmita Behera,Suresh S. Ramalingam,Gabriel Sica,Douglas B. Flieder,Jeff Boyd,Jo Ellen Weaver,Bernard Kohl,Dang Huy Quoc Thinh,George E. Sandusky,Hartmut Juhl,Edwina Duhig,Peter B. Illei,Edward Gabrielson,James Shin,Beverly Lee,Kristen Rogers,Dante Trusty,Malcolm V. Brock,Christina Williamson,Eric J. Burks,Kimberly M. Rieger-Christ,Antonia H. Holway,Travis Sullivan,Michael K. Asiedu,Farhad Kosari,Natasha Rekhtman,Maureen F. Zakowski,Valerie W. Rusch,Paul Zippile,James Suh,Harvey I. Pass,Chandra Goparaju,Yvonne Owusu-Sarpong,John M. S. Bartlett,Sugy Kodeeswaran,Jeremy Parfitt,Harmanjatinder S. Sekhon,Monique Albert,John Eckman,Jerome Myers,Carl Morrison,Carmelo Gaudioso,Jeffrey A. Borgia,Philip Bonomi,Mark Pool,Michael J. Liptay,Fedor Moiseenko,Irina Zaytseva,Hendrik Dienemann,Michael Meister,Philipp A. Schnabel,Thomas Muley,Martin Peifer,Carmen Gomez-Fernandez,Lynn M. Herbert,Sophie C. Egea,Mei Huang,Leigh B. Thorne,Lori Boice,Ashley H. Salazar,William K. Funkhouser,W. Kimryn Rathmell,Rajiv Dhir,Samuel A. Yousem,Sanja Dacic,Frank Schneider,Jill M. Siegfried,Richard A. Hajek,Mark A. Watson,Sandra McDonald,Bryan F. Meyers,Belinda E. Clarke,Ian A. Yang,Kwun M. Fong,Lindy Hunter,Morgan Windsor,Rayleen V. Bowman,Solange Peters,Igor Letovanec,Khurram Z. Khan,Mark A. Jensen,Eric E. Snyder,Deepak Srinivasan,Ari B. Kahn,Julien Baboud,David Pot,Kenna R. Mills Shaw,Margi Sheth,Tanja Davidsen,John A. Demchok,Liming Yang,Zhining Wang,Roy Tarnuzzer,Jean C. Zenklusen,Bradley A. Ozenberger,Heidi J. Sofia,Richard T. Cheney +318 more