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Integrative clinical genomics of advanced prostate cancer.
Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana.
Afiliação
  • Robinson D; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Van Allen EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Wu YM; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Schultz N; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Lonigro RJ; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; Institute for Precision Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; New York Presbyterian Hospital, New York, NY 10021, USA; Meyer Cancer, Weill
  • Montgomery B; Computational Biology Program, Public Health Sciences Division and Basic Science Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA; Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98109, USA.
  • Taplin ME; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Pritchard CC; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
  • Attard G; Cancer Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research, London SM2 5NG, UK; Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
  • Beltran H; Institute for Precision Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; New York Presbyterian Hospital, New York, NY 10021, USA; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; Meyer Cancer, Weill Medical College of Cornel
  • Abida W; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Bradley RK; Computational Biology Program, Public Health Sciences Division and Basic Science Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA.
  • Vinson J; Prostate Cancer Clinical Trials Consortium, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Cao X; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
  • Vats P; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Kunju LP; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Hussain M; Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI
  • Feng FY; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, US
  • Tomlins SA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Depart
  • Cooney KA; Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI
  • Smith DC; Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI
  • Brennan C; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Siddiqui J; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Mehra R; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Chen Y; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urolog
  • Rathkopf DE; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Morris MJ; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA; Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Solomon SB; Interventional Radiology, Department of Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Durack JC; Interventional Radiology, Department of Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Reuter VE; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Gopalan A; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Gao J; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Loda M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology,
  • Lis RT; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Bowden M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA.
  • Balk SP; Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Gaviola G; Department of Musculoskeletal Radiology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Sougnez C; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Gupta M; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Yu EY; Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98109, USA.
  • Mostaghel EA; Computational Biology Program, Public Health Sciences Division and Basic Science Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA; Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98109, USA.
  • Cheng HH; Computational Biology Program, Public Health Sciences Division and Basic Science Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA; Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98109, USA.
  • Mulcahy H; Department of Radiology, University of Washington, Seattle, WA 98109, USA.
  • True LD; Department of Pathology, University of Washington Medical Center, Seattle, WA 98109, USA.
  • Plymate SR; Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98109, USA.
  • Dvinge H; Computational Biology Program, Public Health Sciences Division and Basic Science Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA.
  • Ferraldeschi R; Cancer Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research, London SM2 5NG, UK; Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
  • Flohr P; Cancer Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research, London SM2 5NG, UK; Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
  • Miranda S; Cancer Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research, London SM2 5NG, UK; Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
Cell ; 161(5): 1215-1228, 2015 May 21.
Article em En | MEDLINE | ID: mdl-26000489
ABSTRACT
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, ß-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Perfilação da Expressão Gênica / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Perfilação da Expressão Gênica / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article