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Integrative clinical and molecular characterization of translocation renal cell carcinoma.
Bakouny, Ziad; Sadagopan, Ananthan; Ravi, Praful; Metaferia, Nebiyou Y; Li, Jiao; AbuHammad, Shatha; Tang, Stephen; Denize, Thomas; Garner, Emma R; Gao, Xin; Braun, David A; Hirsch, Laure; Steinharter, John A; Bouchard, Gabrielle; Walton, Emily; West, Destiny; Labaki, Chris; Dudani, Shaan; Gan, Chun-Loo; Sethunath, Vidyalakshmi; Carvalho, Filipe L F; Imamovic, Alma; Ricker, Cora; Vokes, Natalie I; Nyman, Jackson; Berchuck, Jacob E; Park, Jihye; Hirsch, Michelle S; Haq, Rizwan; Mary Lee, Gwo-Shu; McGregor, Bradley A; Chang, Steven L; Feldman, Adam S; Wu, Catherine J; McDermott, David F; Heng, Daniel Y C; Signoretti, Sabina; Van Allen, Eliezer M; Choueiri, Toni K; Viswanathan, Srinivas R.
Afiliação
  • Bakouny Z; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Sadagopan A; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Ravi P; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Metaferia NY; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Li J; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • AbuHammad S; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Tang S; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Denize T; Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Garner ER; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Gao X; Harvard Medical School, Boston, MA, USA; Department of Internal Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
  • Braun DA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Yale Cancer Center / Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Hirsch L; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA.
  • Steinharter JA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Bouchard G; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Walton E; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • West D; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Labaki C; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Dudani S; Division of Medical Oncology/Hematology, William Osler Health System, Brampton, ON, Canada.
  • Gan CL; Division of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
  • Sethunath V; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Carvalho FLF; Division of Urology, Brigham and Women's Hospital, Boston, MA, USA.
  • Imamovic A; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Ricker C; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Vokes NI; Department of Thoracic/Head and Neck Medical Oncology, Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX, USA.
  • Nyman J; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Berchuck JE; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Park J; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hirsch MS; Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Haq R; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Mary Lee GS; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • McGregor BA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Chang SL; Harvard Medical School, Boston, MA, USA; Division of Urology, Brigham and Women's Hospital, Boston, MA, USA.
  • Feldman AS; Department of Urology, Massachusetts General Hospital, Boston, MA, USA.
  • Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • McDermott DF; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Heng DYC; Division of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
  • Signoretti S; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Van Allen EM; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: toni_choueiri@dfci.harvard.edu.
  • Viswanathan SR; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: srinivas.viswanathan@dfci.harvard.edu.
Cell Rep ; 38(1): 110190, 2022 01 04.
Article em En | MEDLINE | ID: mdl-34986355
ABSTRACT
Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to targeted therapies. Consistently, we find that outcomes for patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs) are worse than those treated with immune checkpoint inhibitors (ICI). Using multiparametric immunofluorescence, we find that the tumors are infiltrated with CD8+ T cells, though the T cells harbor an exhaustion immunophenotype distinct from that of clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Proteínas de Fusão Oncogênica / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Fator de Transcrição Associado à Microftalmia / Neoplasias Renais Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Proteínas de Fusão Oncogênica / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Fator de Transcrição Associado à Microftalmia / Neoplasias Renais Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article