UM
Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas
Knijnenburg T.A.7; Wang L.1; Zimmermann M.T.17; Chambwe N.7; Gao G.F.8; Cherniack A.D.8; Fan H.6; Shen H.6; Way G.P.15; Greene C.S.15; Liu Y.1; Akbani R.1; Feng B.10; Donehower L.A.4; Miller C.4; Shen Y.11; Karimi M.11; Chen H.11; Kim P.16; Jia P.16; Shinbrot E.4; Zhang S.1; Liu J.5; Hu H.5; Bailey M.H.2; Yau C.13; Wolf D.13; Zhao Z.16; Weinstein J.N.1; Li L.1; Ding L.2; Mills G.B.1; Laird P.W.6; Wheeler D.A.4; Shmulevich I.7; Caesar-Johnson S.J.; Demchok J.A.; Felau I.; Kasapi M.; Ferguson M.L.; Hutter C.M.; Sofia H.J.; Tarnuzzer R.; Wang Z.; Yang L.; Zenklusen J.C.; Zhang J.J.; Chudamani S.; Lolla L.; Naresh R.; Pihl T.; Sun Q.; Wan Y.; Wu Y.; Cho J.; DeFreitas T.; Frazer S.; Gehlenborg N.; Getz G.; Heiman D.I.; Kim J.; Lawrence M.S.; Lin P.; Meier S.; Noble M.S.; Saksena G.; Voet D.; Zhang H.; Bernard B.; Dhankani V.; Knijnenburg T.; Kramer R.; Leinonen K.; Miller M.; Reynolds S.; Thorsson V.; Zhang W.; Broom B.M.; Hegde A.M.; Ju Z.; Kanchi R.S.; Korkut A.; Li J.; Liang H.; Ling S.; Liu W.; Lu Y.; Ng K.-S.; Rao A.; Ryan M.; Wang J.; Zhang J.; Abeshouse A.; Armenia J.; Chakravarty D.; Chatila W.K.; de Bruijn I.; Gao J.; Gross B.E.; Heins Z.J.; Kundra R.; La K.; Ladanyi M.; Luna A.; Nissan M.G.; Ochoa A.; Phillips S.M.; Reznik E.; Sanchez-Vega F.; Sander C.; Schultz N.; Sheridan R.; Sumer S.O.; Sun Y.; Taylor B.S.; Anur P.; Peto M.; Spellman P.; Benz C.; Stuart J.M.; Wong C.K.; Hayes D.N.; Parker J.S.; Wilkerson M.D.; Ally A.; Balasundaram M.; Bowlby R.; Brooks D.; Carlsen R.; Chuah E.; Dhalla N.; Holt R.; Jones S.J.M.; Kasaian K.; Lee D.; Ma Y.; Marra M.A.; Mayo M.; Moore R.A.; Mungall A.J.; Mungall K.; Robertson A.G.; Sadeghi S.; Schein J.E.; Sipahimalani P.; Tam A.; Thiessen N.; Tse K.; Wong T.; Berger A.C.; Beroukhim R.; Cibulskis C.; Gabriel S.B.; Ha G.; Meyerson M.; Schumacher S.E.; Shih J.; Kucherlapati M.H.; Kucherlapati R.S.; Baylin S.; Cope L.; Danilova L.; Bootwalla M.S.; Lai P.H.; Maglinte D.T.; Van Den Berg D.J.; Weisenberger D.J.; Auman J.T.; Balu S.; Bodenheimer T.; Fan C.; Hoadley K.A.; Hoyle A.P.; Jefferys S.R.; Jones C.D.; Meng S.; Mieczkowski P.A.; Mose L.E.; Perou A.H.; Perou C.M.; Roach J.; Shi Y.; Simons J.V.; Skelly T.; Soloway M.G.; Tan D.; Veluvolu U.; Hinoue T.; Zhou W.; Bellair M.; Chang K.; Covington K.; Creighton C.J.; Dinh H.; Doddapaneni H.; Drummond J.; Gibbs R.A.; Glenn R.; Hale W.; Han Y.; Hu J.; Korchina V.; Lee S.; Lewis L.; Li W.; Liu X.; Morgan M.; Morton D.; Muzny D.; Santibanez J.; Sheth M.; Wang M.; Xi L.; Zhao F.; Hess J.; Appelbaum E.L.; Bailey M.; Cordes M.G.; Fronick C.C.; Fulton L.A.; Fulton R.S.; Kandoth C.; Mardis E.R.; McLellan M.D.; Miller C.A.; Schmidt H.K.; Wilson R.K.; Crain D.; Curley E.; Gardner J.; Lau K.; Mallery D.; Morris S.; Paulauskis J.; Penny R.; Shelton C.; Shelton T.; Sherman M.; Thompson E.; Yena P.; Bowen J.; Gastier-Foster J.M.; Gerken M.; Leraas K.M.; Lichtenberg T.M.; Ramirez N.C.; Wise L.; Zmuda E.; Corcoran N.; Costello T.; Hovens C.; Carvalho A.L.; de Carvalho A.C.; Fregnani J.H.; Longatto-Filho A.; Reis R.M.; Scapulatempo-Neto C.; Silveira H.C.S.; Vidal D.O.; Burnette A.; Eschbacher J.; Hermes B.; Noss A.; Singh R.; Anderson M.L.; Castro P.D.; Ittmann M.; Huntsman D.; Kohl B.; Le X.; Thorp R.; Andry C.; Duffy E.R.; Lyadov V.; Paklina O.; Setdikova G.; Shabunin A.; Tavobilov M.; McPherson C.; Warnick R.; Berkowitz R.; Cramer D.; Feltmate C.; Horowitz N.; Kibel A.; Muto M.; Raut C.P.; Malykh A.; Barnholtz-Sloan J.S.; Barrett W.; Devine K.; Fulop J.; Ostrom Q.T.; Shimmel K.; Wolinsky Y.; Sloan A.E.; De Rose A.; Giuliante F.; Goodman M.; Karlan B.Y.; Hagedorn C.H.; Eckman J.; Harr J.; Myers J.; Tucker K.; Zach L.A.; Deyarmin B.; Kvecher L.; Larson C.; Mural R.J.; Somiari S.; Vicha A.; Zelinka T.; Bennett J.; Iacocca M.; Rabeno B.; Swanson P.; Latour M.; Lacombe L.; Tetu B.; Bergeron A.; McGraw M.; Staugaitis S.M.; Chabot J.; Hibshoosh H.; Sepulveda A.; Su T.; Wang T.; Potapova O.; Voronina O.; Desjardins L.; Mariani O.; Roman-Roman S.; Sastre X.; Stern M.-H.; Cheng F.; Signoretti S.; Berchuck A.; Bigner D.; Lipp E.; Marks J.; McCall S.; McLendon R.; Secord A.; Sharp A.; Behera M.; Brat D.J.; Chen A.; Delman K.; Force S.; Khuri F.; Magliocca K.; Maithel S.; Olson J.J.; Owonikoko T.; Pickens A.; Ramalingam S.; Shin D.M.; Sica G.; Van Meir E.G.; Zhang H.; Eijckenboom W.; Gillis A.; Korpershoek E.; Looijenga L.; Oosterhuis W.; Stoop H.; van Kessel K.E.; Zwarthoff E.C.; Calatozzolo C.; Cuppini L.; Cuzzubbo S.; DiMeco F.; Finocchiaro G.; Mattei L.; Perin A.; Pollo B.; Chen C.; Houck J.; Lohavanichbutr P.; Hartmann A.; Stoehr C.; Stoehr R.; Taubert H.; Wach S.; Wullich B.; Kycler W.; Murawa D.; Wiznerowicz M.; Chung K.; Edenfield W.J.; Martin J.; Baudin E.; Bubley G.; Bueno R.; De Rienzo A.; Richards W.G.; Kalkanis S.; Mikkelsen T.; Noushmehr H.; Scarpace L.; Girard N.; Aymerich M.; Campo E.; Gine E.; Guillermo A.L.; Van Bang N.; Hanh P.T.; Phu B.D.; Tang Y.; Colman H.; Evason K.; Dottino P.R.; Martignetti J.A.; Gabra H.; Juhl H.; Akeredolu T.; Stepa S.; Hoon D.; Ahn K.; Kang K.J.; Beuschlein F.; Breggia A.; Birrer M.; Bell D.; Borad M.; Bryce A.H.; Castle E.; Chandan V.; Cheville J.; Copland J.A.; Farnell M.; Flotte T.; Giama N.; Ho T.; Kendrick M.; Kocher J.-P.; Kopp K.; Moser C.; Nagorney D.; O'Brien D.; O'Neill B.P.; Patel T.; Petersen G.; Que F.; Rivera M.; Roberts L.; Smallridge R.; Smyrk T.; Stanton M.; Thompson R.H.; Torbenson M.; Yang J.D.; Zhang L.; Brimo F.; Ajani J.A.; Gonzalez A.M.A.; Behrens C.; Bondaruk J.; Broaddus R.; Czerniak B.; Esmaeli B.; Fujimoto J.; Gershenwald J.; Guo C.; Lazar A.J.; Logothetis C.; Meric-Bernstam F.; Moran C.; Ramondetta L.; Rice D.; Sood A.; Tamboli P.; Thompson T.; Troncoso P.; Tsao A.; Wistuba I.; Carter C.; Haydu L.; Hersey P.; Jakrot V.; Kakavand H.; Kefford R.; Lee K.; Long G.; Mann G.; Quinn M.; Saw R.; Scolyer R.; Shannon K.; Spillane A.; Stretch J.; Synott M.; Thompson J.; Wilmott J.; Al-Ahmadie H.; Chan T.A.; Ghossein R.; Gopalan A.; Levine D.A.; Reuter V.; Singer S.; Singh B.; Tien N.V.; Broudy T.; Mirsaidi C.; Nair P.; Drwiega P.; Miller J.; Smith J.; Zaren H.; Park J.-W.; Hung N.P.; Kebebew E.; Linehan W.M.; Metwalli A.R.; Pacak K.; Pinto P.A.; Schiffman M.; Schmidt L.S.; Vocke C.D.; Wentzensen N.; Worrell R.; Yang H.; Moncrieff M.; Goparaju C.; Melamed J.; Pass H.; Botnariuc N.; Caraman I.; Cernat M.; Chemencedji I.; Clipca A.; Doruc S.; Gorincioi G.; Mura S.; Pirtac M.; Stancul I.; Tcaciuc D.; Albert M.; Alexopoulou I.; Arnaout A.; Bartlett J.; Engel J.; Gilbert S.; Parfitt J.; Sekhon H.; Thomas G.; Rassl D.M.; Rintoul R.C.; Bifulco C.; Tamakawa R.; Urba W.; Hayward N.; Timmers H.; Antenucci A.; Facciolo F.; Grazi G.; Marino M.; Merola R.; de Krijger R.; Gimenez-Roqueplo A.-P.; Piche A.; Chevalier S.; McKercher G.; Birsoy K.; Barnett G.; Brewer C.; Farver C.; Naska T.; Pennell N.A.; Raymond D.; Schilero C.; Smolenski K.; Williams F.; Morrison C.; Borgia J.A.; Liptay M.J.; Pool M.; Seder C.W.; Junker K.; Omberg L.; Dinkin M.; Manikhas G.; Alvaro D.; Bragazzi M.C.; Cardinale V.; Carpino G.; Gaudio E.; Chesla D.; Cottingham S.; Dubina M.; Moiseenko F.; Dhanasekaran R.; Becker K.-F.; Janssen K.-P.; Slotta-Huspenina J.; Abdel-Rahman M.H.; Aziz D.; Bell S.; Cebulla C.M.; Davis A.; Duell R.; Elder J.B.; Hilty J.; Kumar B.; Lang J.; Lehman N.L.; Mandt R.; Nguyen P.; Pilarski R.; Rai K.; Schoenfield L.; Senecal K.; Wakely P.; Hansen P.; Lechan R.; Powers J.; Tischler A.; Grizzle W.E.; Sexton K.C.; Kastl A.; Henderson J.; Porten S.; Waldmann J.; Fassnacht M.; Asa S.L.; Schadendorf D.; Couce M.; Graefen M.; Huland H.; Sauter G.; Schlomm T.; Simon R.; Tennstedt P.; Olabode O.; Nelson M.; Bathe O.; Carroll P.R.; Chan J.M.; Disaia P.; Glenn P.; Kelley R.K.; Landen C.N.; Phillips J.; Prados M.; Simko J.; Smith-McCune K.; VandenBerg S.; Roggin K.; Fehrenbach A.; Kendler A.; Sifri S.; Steele R.; Jimeno A.; Carey F.; Forgie I.; Mannelli M.; Carney M.; Hernandez B.; Campos B.; Herold-Mende C.; Jungk C.; Unterberg A.; von Deimling A.; Bossler A.; Galbraith J.; Jacobus L.; Knudson M.; Knutson T.; Ma D.; Milhem M.; Sigmund R.; Godwin A.K.; Madan R.; Rosenthal H.G.; Adebamowo C.; Adebamowo S.N.; Boussioutas A.; Beer D.; Giordano T.; Mes-Masson A.-M.; Saad F.; Bocklage T.; Landrum L.; Mannel R.; Moore K.; Moxley K.; Postier R.; Walker J.; Zuna R.; Feldman M.; Valdivieso F.; Dhir R.; Luketich J.; Pinero E.M.M.; Quintero-Aguilo M.; Carlotti C.G.; Dos Santos J.S.; Kemp R.; Sankarankuty A.; Tirapelli D.; Catto J.; Agnew K.; Swisher E.; Creaney J.; Robinson B.; Shelley C.S.; Godwin E.M.; Kendall S.; Shipman C.; Bradford C.; Carey T.; Haddad A.; Moyer J.; Peterson L.; Prince M.; Rozek L.; Wolf G.; Bowman R.; Fong K.M.; Yang I.; Korst R.; Rathmell W.K.; Fantacone-Campbell J.L.; Hooke J.A.; Kovatich A.J.; Shriver C.D.; DiPersio J.; Drake B.; Govindan R.; Heath S.; Ley T.; Van Tine B.; Westervelt P.; Rubin M.A.; Lee J.I.; Aredes N.D.; Mariamidze A.; Monnat R.J.12; Xiao Y.10; Wang C.3
2018-04-03
Source PublicationCell Reports
ISSN22111247
Volume23Issue:1Pages:239-254.e6
AbstractDNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy. Knijnenburg et al. present The Cancer Genome Atlas (TCGA) Pan-Cancer analysis of DNA damage repair (DDR) deficiency in cancer. They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores.
KeywordDNA damage footprints DNA damage repair epigenetic silencing integrative statistical analysis mutational signatures protein structure analysis somatic copy-number alterations somatic mutations The Cancer Genome Atlas PanCanAtlas project
DOI10.1016/j.celrep.2018.03.076
URLView the original
Language英語
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Cited Times [WOS]:122   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Texas MD Anderson Cancer Center
2.Washington University in St. Louis
3.Mayo Medical School
4.Baylor College of Medicine
5.Chan Soon-Shiong Institute of Molecular Medicine at Windber
6.Van Andel Research Institute
7.Institute for Systems Biology
8.Broad Institute
9.Buck Institute for Age Research
10.TESARO, Inc.
11.Texas A and M University
12.University of Washington, Seattle
13.University of California, San Francisco
14.Washington University School of Medicine in St. Louis
15.University of Pennsylvania
16.University of Texas Health Science Center at Houston
17.Medical College of Wisconsin
Recommended Citation
GB/T 7714
Knijnenburg T.A.,Wang L.,Zimmermann M.T.,et al. Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas[J]. Cell Reports,2018,23(1):239-254.e6.
APA Knijnenburg T.A..,Wang L..,Zimmermann M.T..,Chambwe N..,Gao G.F..,...&Wang C..(2018).Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas.Cell Reports,23(1),239-254.e6.
MLA Knijnenburg T.A.,et al."Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas".Cell Reports 23.1(2018):239-254.e6.
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