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Subtype heterogeneity and epigenetic convergence in neuroendocrine prostate cancer.
Cejas, Paloma; Xie, Yingtian; Font-Tello, Alba; Lim, Klothilda; Syamala, Sudeepa; Qiu, Xintao; Tewari, Alok K; Shah, Neel; Nguyen, Holly M; Patel, Radhika A; Brown, Lisha; Coleman, Ilsa; Hackeng, Wenzel M; Brosens, Lodewijk; Dreijerink, Koen M A; Ellis, Leigh; Alaiwi, Sarah Abou; Seo, Ji-Heui; Baca, Sylvan; Beltran, Himisha; Khani, Francesca; Pomerantz, Mark; Dall'Agnese, Alessandra; Crowdis, Jett; Van Allen, Eliezer M; Bellmunt, Joaquim; Morrisey, Colm; Nelson, Peter S; DeCaprio, James; Farago, Anna; Dyson, Nicholas; Drapkin, Benjamin; Liu, X Shirley; Freedman, Matthew; Haffner, Michael C; Corey, Eva; Brown, Myles; Long, Henry W.
Afiliação
  • Cejas P; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA. paloma_cejas@dfci.harvard.edu.
  • Xie Y; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA. paloma_cejas@dfci.harvard.edu.
  • Font-Tello A; Translational Oncology Laboratory, Hospital La Paz Institute for Health Research (IdiPAZ) and CIBERONC, La Paz University Hospital, Madrid, Spain. paloma_cejas@dfci.harvard.edu.
  • Lim K; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Syamala S; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Qiu X; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Tewari AK; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Shah N; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Nguyen HM; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Patel RA; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Brown L; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Coleman I; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Hackeng WM; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Brosens L; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Dreijerink KMA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ellis L; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Alaiwi SA; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Seo JH; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Baca S; Department of Urology, University of Washington, Seattle, WA, USA.
  • Beltran H; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Khani F; Department of Urology, University of Washington, Seattle, WA, USA.
  • Pomerantz M; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Dall'Agnese A; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Crowdis J; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Van Allen EM; Department of Endocrinology, Amsterdam UMC, Amsterdam, The Netherlands.
  • Bellmunt J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Morrisey C; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Nelson PS; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • DeCaprio J; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Farago A; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Dyson N; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Drapkin B; Weill Cornell Medical Center, Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY, USA.
  • Liu XS; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Freedman M; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA.
  • Haffner MC; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Corey E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Brown M; Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
  • Long HW; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Commun ; 12(1): 5775, 2021 10 01.
Article em En | MEDLINE | ID: mdl-34599169
ABSTRACT
Neuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes of a range of human NECs and show convergence to the activation of a common epigenetic program. With a particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), we analyze cell lines, patient-derived xenograft (PDX) models and human clinical samples to show the existence of two distinct NEPC subtypes based on the expression of the neuronal transcription factors ASCL1 and NEUROD1. While in cell lines and PDX models these subtypes are mutually exclusive, single-cell analysis of human clinical samples exhibits a more complex tumor structure with subtypes coexisting as separate sub-populations within the same tumor. These tumor sub-populations differ genetically and epigenetically contributing to intra- and inter-tumoral heterogeneity in human metastases. Overall, our results provide a deeper understanding of the shared clinicopathological characteristics shown by NECs. Furthermore, the intratumoral heterogeneity of human NEPCs suggests the requirement of simultaneous targeting of coexisting tumor populations as a therapeutic strategy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Fatores de Transcrição / Carcinoma Neuroendócrino Tipo de estudo: Prognostic_studies Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Fatores de Transcrição / Carcinoma Neuroendócrino Tipo de estudo: Prognostic_studies Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos