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Prostate cancer reactivates developmental epigenomic programs during metastatic progression.
Pomerantz, Mark M; Qiu, Xintao; Zhu, Yanyun; Takeda, David Y; Pan, Wenting; Baca, Sylvan C; Gusev, Alexander; Korthauer, Keegan D; Severson, Tesa M; Ha, Gavin; Viswanathan, Srinivas R; Seo, Ji-Heui; Nguyen, Holly M; Zhang, Baohui; Pasaniuc, Bogdan; Giambartolomei, Claudia; Alaiwi, Sarah A; Bell, Connor A; O'Connor, Edward P; Chabot, Matthew S; Stillman, David R; Lis, Rosina; Font-Tello, Alba; Li, Lewyn; Cejas, Paloma; Bergman, Andries M; Sanders, Joyce; van der Poel, Henk G; Gayther, Simon A; Lawrenson, Kate; Fonseca, Marcos A S; Reddy, Jessica; Corona, Rosario I; Martovetsky, Gleb; Egan, Brian; Choueiri, Toni; Ellis, Leigh; Garraway, Isla P; Lee, Gwo-Shu Mary; Corey, Eva; Long, Henry W; Zwart, Wilbert; Freedman, Matthew L.
Afiliación
  • Pomerantz MM; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Qiu X; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zhu Y; Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Takeda DY; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Pan W; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA.
  • Baca SC; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Gusev A; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Korthauer KD; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Severson TM; Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ha G; Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Viswanathan SR; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Seo JH; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Nguyen HM; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zhang B; Department of Urology, University of Washington, Seattle, WA, USA.
  • Pasaniuc B; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Giambartolomei C; Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA.
  • Alaiwi SA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Bell CA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • O'Connor EP; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Chabot MS; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Stillman DR; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Lis R; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Font-Tello A; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Li L; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Cejas P; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Bergman AM; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Sanders J; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • van der Poel HG; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Gayther SA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Lawrenson K; Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Fonseca MAS; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Reddy J; Department of Urology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Corona RI; Division of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Martovetsky G; Department of Urology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Egan B; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Choueiri T; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ellis L; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Garraway IP; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lee GM; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Corey E; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Long HW; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Zwart W; Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Freedman ML; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Nat Genet ; 52(8): 790-799, 2020 08.
Article en En | MEDLINE | ID: mdl-32690948
Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos