Journal ArticleDOI
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Peter C.C. Fong,D. S. Boss,Timothy A. Yap,Andrew Tutt,Peijun Wu,Marja Mergui-Roelvink,Peter S. Mortimer,Helen Swaisland,Alan Lau,Mark J. O'Connor,Alan Ashworth,James Carmichael,Stan B. Kaye,Jan H.M. Schellens,Jan H.M. Schellens,Johann S. de Bono +15 more
TLDR
Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCa2 mutation.Abstract:
Background The inhibition of poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) is a potential synthetic lethal therapeutic strategy for the treatment of cancers with specific DNA-repair defects, including those arising in carriers of a BRCA1 or BRCA2 mutation. We conducted a clinical evaluation in humans of olaparib (AZD2281), a novel, potent, orally active PARP inhibitor. Methods This was a phase 1 trial that included the analysis of pharmacokinetic and pharmacodynamic characteristics of olaparib. Selection was aimed at having a study population enriched in carriers of a BRCA1 or BRCA2 mutation. Results We enrolled and treated 60 patients; 22 were carriers of a BRCA1 or BRCA2 mutation and 1 had a strong family history of BRCA-associated cancer but declined to undergo mutational testing. The olaparib dose and schedule were increased from 10 mg daily for 2 of every 3 weeks to 600 mg twice daily continuously. Reversible dose-limiting toxicity was seen in one of eight patients receiving 400 mg twice...read more
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Comprehensive molecular portraits of human breast tumours
Daniel C. Koboldt,Robert S. Fulton,Michael D. McLellan,Heather Schmidt,Joelle Kalicki-Veizer,Joshua F. McMichael,Lucinda Fulton,David J. Dooling,Li Ding,Elaine R. Mardis,Richard K. Wilson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Rebecca Carlsen,Candace Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Jacqueline E. Schein,Arash Shafiei,Payal Sipahimalani,Jared R. Slobodan,Dominik Stoll,Angela Tam,Nina Thiessen,Richard Varhol,Natasja Wye,Thomas Zeng,Yongjun Zhao,Inanc Birol,Steven J.M. Jones,Marco A. Marra,Andrew D. Cherniack,Gordon Saksena,Gordon Saksena,Robert C. Onofrio,Nam H. Pho,Scott L. Carter,Steven E. Schumacher,Steven E. Schumacher,Barbara Tabak,Barbara Tabak,Bryan Hernandez,Jeff Gentry,Huy Nguyen,Andrew Crenshaw,Kristin G. Ardlie,Rameen Beroukhim,Rameen Beroukhim,Wendy Winckler,Gad Getz,Gad Getz,Stacey Gabriel,Matthew Meyerson,Matthew Meyerson,Lynda Chin,Lynda Chin,Raju Kucherlapati,Katherine A. Hoadley,J. Todd Auman,Cheng Fan,Yidi J. Turman,Yan Shi,Ling Li,Michael D. Topal,Xiaping He,Hann Hsiang Chao,Aleix Prat,Grace O. Silva,Michael D. Iglesia,Wei Zhao,Jerry Usary,Jonathan S. Berg,Michael C. Adams,Jessica K. Booker,Junyuan Wu,Anisha Gulabani,Tom Bodenheimer,Alan P. Hoyle,Janae V. Simons,Matthew G. Soloway,Lisle E. Mose,Stuart R. Jefferys,Saianand Balu,Joel S. Parker,D. Neil Hayes,Charles M. Perou,Simeen Malik,Swapna Mahurkar,Hui Shen,Daniel J. Weisenberger,Timothy J. Triche,Phillip H. Lai,Moiz S. Bootwalla,Dennis T. Maglinte,Benjamin P. Berman,David Van Den Berg,Stephen B. Baylin,Peter W. Laird,Chad J. Creighton,Lawrence A. Donehower,Michael S. Noble,Doug Voet,Nils Gehlenborg,Daniel Di Cara,Juinhua Zhang,Hailei Zhang,Chang-Jiun Wu,Spring Yingchun Liu,Michael S. Lawrence,Lihua Zou,Andrey Sivachenko,Pei Lin,Petar Stojanov,Rui Jing,Juok Cho,Raktim Sinha,Richard W. Park,Marc Danie Nazaire,James A. Robinson,Helga Thorvaldsdottir,Jill P. Mesirov,Peter J. Park,Sheila Reynolds,Richard Kreisberg,Brady Bernard,Ryan Bressler,Timo Erkkilä,Jake Lin,Vesteinn Thorsson,Wei Zhang,Ilya Shmulevich,Giovanni Ciriello,Nils Weinhold,Nikolaus Schultz,Jianjiong Gao,Ethan Cerami,Benjamin Gross,Anders Jacobsen,Rileen Sinha,B. Arman Aksoy,Yevgeniy Antipin,Boris Reva,Ronglai Shen,Barry S. Taylor,Marc Ladanyi,Chris Sander,Pavana Anur,Paul T. Spellman,Yiling Lu,Wenbin Liu,Roel R.G. Verhaak,Gordon B. Mills,Gordon B. Mills,Rehan Akbani,Nianxiang Zhang,Bradley M. Broom,Tod D. Casasent,Chris Wakefield,Anna K. Unruh,Keith A. Baggerly,Kevin R. Coombes,John N. Weinstein,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Evan O. Paull,Daniel E. Carlin,Christopher K. Wong,Artem Sokolov,Janita Thusberg,Sean D. Mooney,Sam Ng,Theodore C. Goldstein,Kyle Ellrott,Mia Grifford,Christopher Wilks,Singer Ma,Brian Craft,Chunhua Yan,Ying Hu,Daoud Meerzaman,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Jay Bowen,Nilsa C. Ramirez,Nilsa C. Ramirez,Aaron D. Black,Robert E. Pyatt,Robert E. Pyatt,Peter White,Peter White,Erik Zmuda,Jessica Frick,Tara M. Lichtenberg,Robin Brookens,Myra M. George,Mark Gerken,Hollie A. Harper,Kristen M. Leraas,Lisa Wise,Teresa R. Tabler,Cynthia McAllister,Thomas Barr,Melissa Hart-Kothari,Katie Tarvin,Charles Saller,George E. Sandusky,Colleen Mitchell,Mary Iacocca,Jennifer Brown,Brenda Rabeno,Christine Czerwinski,Nicholas J. Petrelli,Oleg Dolzhansky,Mikhail Abramov,Olga Voronina,Olga Potapova,Jeffrey R. Marks,Wiktoria Maria Suchorska,Dawid Murawa,Witold Kycler,Matthew Ibbs,Konstanty Korski,Arkadiusz Spychała,Pawel Murawa,Jacek J. Brzeziński,Hanna Perz,Radoslaw Łaźniak,M. Teresiak,Honorata Tatka,Ewa Leporowska,Marta Bogusz-Czerniewicz,Julian Malicki,Andrzej Mackiewicz,Maciej Wiznerowicz,Xuan Van Le,Bernard Kohl,Nguyen Viet Tien,Richard Thorp,Nguyen Van Bang,Howard H. Sussman,Bui Duc Phu,Richard A. Hajek,Nguyen Phi Hung,Huynh Quyet Thang,Khurram Z. Khan,Robert Penny,David Mallery,Erin Curley,Candace Shelton,Peggy Yena,James N. Ingle,Fergus J. Couch,Wilma L. Lingle,Tari A. King,Ana M. Gonzalez-Angulo,Ana M. Gonzalez-Angulo,Mary D. Dyer,Shuying Liu,Xiaolong Meng,Modesto Patangan,Frederic Waldman,Frederic Waldman,Hubert Stoppler,W. Kimryn Rathmell,Leigh B. Thorne,Mei Huang,Lori Boice,Ashley Hill,Carl Morrison,Carmelo Gaudioso,Wiam Bshara,Kelly Daily,Sophie C. Egea,Mark D. Pegram,Carmen Gomez-Fernandez,Rajiv Dhir,Rohit Bhargava,Adam Brufsky,Craig D. Shriver,Jeffrey A. Hooke,Jamie Leigh Campbell,Richard J. Mural,Hai Hu,Stella Somiari,Caroline Larson,Brenda Deyarmin,Leonid Kvecher,Albert J. Kovatich,Matthew J. Ellis,Thomas Stricker,Kevin P. White,Olufunmilayo I. Olopade,Chunqing Luo,Yaqin Chen,Ron Bose,Li-Wei Chang,Andrew H. Beck,Todd Pihl,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Brenda Ayala,Mark Backus,Jessica Walton,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,David Pot,Margi Sheth,John A. Demchok,Kenna R. Mills Shaw,Liming Yang,Greg Eley,Martin L. Ferguson,Roy Tarnuzzer,Jiashan Zhang,Laura A.L. Dillon,Kenneth H. Buetow,Peter Fielding,Bradley A. Ozenberger,Mark S. Guyer,Heidi J. Sofia,Jacqueline D. Palchik +355 more
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Journal ArticleDOI
Integrated genomic analyses of ovarian carcinoma
Debra A. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,M. Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Beth Y. Karlan,Douglas A. Levine,Douglas A. Levine,Douglas A. Levine,Gordon B. Mills,Gordon B. Mills,Carl Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,J. A. Drummond,G. Fowler,Preethi H. Gunaratne,A. C. Hawes,C. L. Kovar,L. R. Lewis,M. B. Morgan,I. F. Newsham,J. Santibanez,Jeffrey G. Reid,L. R. Trevino,Yue Wu,M. Wang,Donna M. Muzny,D. A. Wheeler,Richard A. Gibbs,Gad Getz,Gad Getz,Michael S. Lawrence,Michael S. Lawrence,Kristian Cibulskis,Kristian Cibulskis,Andrey Sivachenko,C. Sougnez,Douglas Voet,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,Kristin G. Ardlie,T. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,M. O'Laughlin,D. J. Dooling,Linnea Fulton,R. Abbott,N. D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Hayden R. Schmidt,Joelle Kalicki,K. D. Delehaunty,Catrina Fronick,Ryan Demeter,L. Cook,J. W. Wallis,L. Lin,Vincent Magrini,J. S. Hodges,James M. Eldred,S. M. Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,R. G.W. Verhaak,Suzie Carter,Craig H. Mermel,G. Saksena,G. Saksena,H. Nguyen,R. C. Onofrio,D. Hubbard,S. Gupta,A. Crenshaw,A. H. Ramos,Lynda Chin,Lynda Chin,Alexei Protopopov,Jinghui Zhang,Jinghui Zhang,Jinghui Zhang,T. M. Kim,Ilana Perna,Y. Xiao,Hailei Zhang,Gang Ren,N. Sathiamoorthy,R. W. Park,R. W. Park,Eunjung Lee,Peter J. Park,Peter J. Park,Raju Kucherlapati,D. M. Absher,L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,L. Cope,James G. Herman,H. Shen,Daniel J. Weisenberger,Houtan Noushmehr,F. Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,J. Buckley,Stephen B. Baylin,Paul T. Spellman,Paul T. Spellman,Elizabeth Purdom,Pierre Neuvial,Pierre Neuvial,Henrik Bengtsson,Henrik Bengtsson,L. R. Jakkula,S. Durinck,S. Durinck,Junhong Han,Junhong Han,S. Dorton,H. Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,J. G. Conboy,Bahram Parvin,H. S. Feiler,Terence P. Speed,Joe W. Gray,Joe W. Gray,N. D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Nikolaus Schultz,L. Borsu,Alex E. Lash,Cameron Brennan,A. Viale,Chris Sander,M. Ladanyi,M. Ladanyi,Katherine A. Hoadley,Katherine A. Hoadley,S. Meng,Y. Du,Y. Du,Yigong Shi,Lulin Li,Y. J. Turman,D. Zang,E. B. Helms,S. Balu,Xiang Zhou,Jane Y. Wu,M. D. Topal,D. N. Hayes,D. N. Hayes,Charles M. Perou,Chaowei Wu,S. Shukla,A. Sivachenko,R. Jing,Yingkai Liu,M. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,A. Olshen,B. Reva,Yevgeniy Antipin,R. Shen,P. Mankoo,Robert L. Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Z. Sanborn,Charles J. Vaske,Jieqing Zhu,Christopher Szeto,G. K. Scott,Christina Yau,Matthew D. Wilkerson,N. Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,T. Shelton,Dirk Grimm,Martha Hatfield,Scott Morris,P. Yena,P. Rhodes,Mark E. Sherman,J. Paulauskis,S. Millis,A. Kahn,John M. Greene,R. Sfeir,M. A. Jensen,John W. Chen,J. Whitmore,S. Alonso,J. Jordan,A. Chu,A. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jane Peterson,Elizabeth J. Thomson +285 more
TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Integrated genomic analyses of ovarian carcinoma
Daphne W. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,Mei Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Douglas A. Levine,Gordon B. Mills,Carolyn A. Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,Jennifer Drummond,Gerald R. Fowler,Preethi H. Gunaratne,Alicia Hawes,Christie Kovar,Lora Lewis,Margaret B. Morgan,Irene Newsham,Jireh Santibanez,Jeffrey G. Reid,Lisa R. Trevino,Yuan Qing Wu,Min Wang,Donna Muzny,D Wheeler,Richard A. Gibbs,Gad Getz,Michael S. Lawrence,Kristian Cibulskis,Andrey Sivachenko,Carrie Sougnez,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,T. J. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,Michelle D O'Laughlin,David J. Dooling,Linnea Fulton,Rachel Abbott,Nathan D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Heather K. Schmidt,Joelle Kalicki,Kimberly D. Delehaunty,Catrina Fronick,Ryan Demeter,Linda S. Cook,John W. Wallis,Ling Lin,Vincent Magrini,Jennifer S. Hodges,James M. Eldred,Shaleigh Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,Roeland Verhaak,Suzie Carter,Craig H. Mermel,Gordon Saksena,Huy V. Nguyen,Robert C. Onofrio,Diana D. Hubbard,Sonal Gupta,Andrew Crenshaw,Alex H. Ramos,Lynda Chin,Alexei Protopopov,Juinhua Zhang,T. M. Kim,Ilana Perna,Yonghong Xiao,Hailei Zhang,Gang Ren,Narayanan Sathiamoorthy,Richard W. Park,Eunjung Lee,Peter J. Park,Raju Kucherlapati,Devin Absher,Lindsay L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,Leslie Cope,James G. Herman,Hui Shen,Daniel J. Weisenberger,Houtan Noushmehr,Fei Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,Jonathan D. Buckley,Stephen B. Baylin,P. Spellman,Elizabeth Purdom,Pierre Neuvial,Henrik Bengtsson,Lakshmi Jakkula,Steffen Durinck,Junhong Han,Shannon Dorton,Henry Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,John G. Conboy,Bahram Parvin,Heidi S. Feiler,Terence P. Speed,Joe W. Gray,Nicholas D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Laetitia Borsu,Alex E. Lash,Cameron Brennan,Agnes Viale,Chris Sander,M. Ladanyi,Katherine A. Hoadley,Shaowu Meng,Ying Du,Yan Shi,Lulin Li,Yidi J. Turman,D. Zang,E. B. Helms,Saianand Balu,Xiang Zhou,Jane Y. Wu,Michael D. Topal,David N. Hayes,Charles M. Perou,Junihua Zhang,Chaowei Wu,Sachet A. Shukla,Andrey Sivachenko,Rui Jing,Yingkai Liu,Michael S. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,Adam B. Olshen,Boris Reva,Yevgeniy Antipin,Ronglai Shen,Parminder K. Mankoo,Rachael Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,John Zachary Sanborn,Charles J. Vaske,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Matthew D. Wilkerson,Nianxiang Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,Troy Shelton,Dirk Grimm,Martha Hatfield,Shannon R. Morris,Peggy Yena,P. Rhodes,Mark E. Sherman,Joseph Paulauskis,S. Millis,Ari B. Kahn,John M. Greene,Robert Sfeir,Mark A. Jensen,John W. Chen,Jon Whitmore,Shelley Alonso,Justin T. Jordan,Anna L. Chu,Jinghui Zhang,Anna D. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jessica L. Peterson,E. Thomson +261 more
TL;DR: The Cancer Genome Atlas project has analyzed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours as mentioned in this paper.
Journal ArticleDOI
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies
Brian D. Lehmann,Joshua A. Bauer,Xi Chen,Melinda E. Sanders,A. Bapsi Chakravarthy,Yu Shyr,Jennifer A. Pietenpol +6 more
TL;DR: Gen expression profiles from 21 breast cancer data sets and identified 587 TNBC cases may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies.
Journal ArticleDOI
Triple-negative breast cancer.
TL;DR: Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer.
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