Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation
Maura Costello,Trevor J. Pugh,Timothy Fennell,Chip Stewart,Lee Lichtenstein,James Meldrim,Jennifer L. Fostel,Dennis C. Friedrich,Danielle Perrin,Danielle Dionne,Sharon Kim,Stacey Gabriel,Eric S. Lander,Sheila Fisher,Gad Getz +14 more
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TLDR
The discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data is described and informatics methods are presented to confidently filter these artifacts from sequencing data sets.Abstract:
As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.read more
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The Somatic Genomic Landscape of Glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neill,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM.
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Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Journal ArticleDOI
Integrated Genomic Characterization of Papillary Thyroid Carcinoma
Nishant Agrawal,Rehan Akbani,B. Arman Aksoy,Adrian Ally,Harindra Arachchi,Sylvia L. Asa,J. Todd Auman,Miruna Balasundaram,Saianand Balu,Stephen B. Baylin,Madhusmita Behera,Brady Bernard,Rameen Beroukhim,Justin A. Bishop,Aaron D. Black,Tom Bodenheimer,Lori Boice,Moiz S. Bootwalla,Jay Bowen,Reanne Bowlby,Christopher A. Bristow,Robin Brookens,Denise Brooks,Robert Bryant,Elizabeth Buda,Yaron S.N. Butterfield,Tobias Carling,Rebecca Carlsen,Scott L. Carter,Sally E. Carty,Timothy A. Chan,Amy Chen,Andrew D. Cherniack,Dorothy Cheung,Lynda Chin,Juok Cho,Andy Chu,Eric Chuah,Kristian Cibulskis,Giovanni Ciriello,Amanda Clarke,Gary L. Clayman,Leslie Cope,John A. Copland,Kyle R. Covington,Ludmila Danilova,Tanja Davidsen,John A. Demchok,Daniel DiCara,Noreen Dhalla,Rajiv Dhir,Sheliann S. Dookran,Gideon Dresdner,Jonathan V. Eldridge,Greg Eley,Adel K El-Naggar,Stephanie Eng,James A. Fagin,Timothy R. Fennell,Robert L. Ferris,Sheila Fisher,Scott Frazer,Jessica Frick,Stacey Gabriel,Ian Ganly,Jianjiong Gao,Levi A. Garraway,Julie M. Gastier-Foster,Gad Getz,Nils Gehlenborg,Ronald Ghossein,Richard A. Gibbs,Thomas J. Giordano,Karen Gomez-Hernandez,Jonna Grimsby,Benjamin Gross,Ranabir Guin,Angela Hadjipanayis,Hollie A. Harper,D. Neil Hayes,David I. Heiman,James G. Herman,Katherine A. Hoadley,Matan Hofree,Robert A. Holt,Alan P. Hoyle,Franklin W. Huang,Mei Huang,Carolyn M. Hutter,Trey Ideker,Lisa Iype,Anders Jacobsen,Stuart R. Jefferys,Corbin D. Jones,Steven J.M. Jones,Katayoon Kasaian,Electron Kebebew,Fadlo R. Khuri,Jaegil Kim,Roger Kramer,Richard Kreisberg,Raju Kucherlapati,David J. Kwiatkowski,Marc Ladanyi,Phillip H. Lai,Peter W. Laird,Eric S. Lander,Michael S. Lawrence,Darlene Lee,Eunjung Lee,Semin Lee,William Lee,Kristen M. Leraas,Tara M. Lichtenberg,Lee Lichtenstein,Pei Lin,Shiyun Ling,Jinze Liu,Wen-Bin Liu,Yingchun Liu,Virginia A. LiVolsi,Yiling Lu,Yussanne Ma,Harshad S. Mahadeshwar,Marco A. Marra,Michael Mayo,David G. McFadden,Shaowu Meng,Matthew Meyerson,Piotr A. Mieczkowski,Michael L. Miller,Gordon B. Mills,Richard A. Moore,Lisle E. Mose,Andrew J. Mungall,Bradley A. Murray,Yuri E. Nikiforov,Michael S. Noble,Akinyemi I. Ojesina,Taofeek K. Owonikoko,Bradley A. Ozenberger,Angeliki Pantazi,Michael Parfenov,Peter J. Park,Joel S. Parker,Evan O. Paull,Chandra Sekhar Pedamallu,Charles M. Perou,Jan F. Prins,Alexei Protopopov,Suresh Ramalingam,Nilsa C. Ramirez,Ricardo Ramirez,Benjamin J. Raphael,W. Kimryn Rathmell,Xiaojia Ren,Sheila Reynolds,Esther Rheinbay,Matthew D. Ringel,Michael Rivera,Jeffrey Roach,A. Gordon Robertson,Mara Rosenberg,Matthew Rosenthal,Sara Sadeghi,Gordon Saksena,Chris Sander,Netty Santoso,Jacqueline E. Schein,Nikolaus Schultz,Steven E. Schumacher,Raja R. Seethala,Jonathan G. Seidman,Yasin Senbabaoglu,Sahil Seth,Samantha Sharpe,Kenna R. Mills Shaw,John Paul Shen,Ronglai Shen,Steven I. Sherman,Margi Sheth,Yan Shi,Ilya Shmulevich,Gabriel Sica,Janae V. Simons,Rileen Sinha,Payal Sipahimalani,Robert C. Smallridge,Heidi J. Sofia,Matthew G. Soloway,Xingzhi Song,Carrie Sougnez,Chip Stewart,Petar Stojanov,Joshua M. Stuart,S. Onur Sumer,Yichao Sun,Barbara Tabak,Angela Tam,Donghui Tan,Jiabin Tang,Roy Tarnuzzer,Barry S. Taylor,Nina Thiessen,Leigh B. Thorne,Vesteinn Thorsson,R. Michael Tuttle,Christopher B. Umbricht,David Van Den Berg,Fabio Vandin,Umadevi Veluvolu,Roeland Verhaak,Michelle Vinco,Doug Voet,Vonn Walter,Zhining Wang,Scot Waring,Paul M. Weinberger,Nils Weinhold,John N. Weinstein,Daniel J. Weisenberger,David A. Wheeler,Matthew D. Wilkerson,Jocelyn Wilson,Michelle D. Williams,Daniel A. Winer,Lisa Wise,Junyuan Wu,Liu Xi,Andrew Wei Xu,Liming Yang,Lixing Yang,Travis I. Zack,Martha A. Zeiger,Dong Zeng,Jean C. Zenklusen,Ni Zhao,Hailei Zhang,Jianhua Zhang,Jiashan Zhang,Wei Zhang,Erik Zmuda,Lihua Zou +242 more
TL;DR: The genomic landscape of 496 PTCs is described and a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties is proposed, which has the potential to improve their pathological classification and better inform the management of the disease.
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