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SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer.
Li, Lianjie; Shen, Chuan; Nakamura, Eijiro; Ando, Kiyohiro; Signoretti, Sabina; Beroukhim, Rameen; Cowley, Glenn S; Lizotte, Patrick; Liberzon, Ella; Bair, Steven; Root, David E; Tamayo, Pablo; Tsherniak, Aviad; Cheng, Su-Chun; Tabak, Barbara; Jacobsen, Anders; Hakimi, A Ari; Schultz, Nikolaus; Ciriello, Giovanni; Sander, Chris; Hsieh, James J; Kaelin, William G.
Afiliación
  • Li L; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Shen C; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Nakamura E; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Ando K; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Signoretti S; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Beroukhim R; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Medi
  • Cowley GS; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Lizotte P; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Liberzon E; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Bair S; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Root DE; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Tamayo P; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Tsherniak A; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Cheng SC; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Tabak B; Department of Cancer Biology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Jacobsen A; Department of Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA.
  • Hakimi AA; Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA.
  • Schultz N; Department of Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA.
  • Ciriello G; Department of Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA.
  • Sander C; Department of Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA.
  • Hsieh JJ; Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA; Department of Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 16605, USA.
  • Kaelin WG; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142,
Cancer Cell ; 24(6): 738-50, 2013 Dec 09.
Article en En | MEDLINE | ID: mdl-24332042
ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and is often linked to loss of chromosome 3p, which harbors the VHL tumor suppressor gene, loss of chromosome 14q, which includes HIF1A, and gain of chromosome 5q. The relevant target(s) on chromosome 5q is not known. Here, we show that 5q amplification leads to overexpression of the SQSTM1 oncogene in ccRCC lines and tumors. Overexpression of SQSTM1 in ccRCC lines promoted resistance to redox stress and increased soft agar growth, while downregulation of SQSTM1 decreased resistance to redox stress, impaired cellular fitness, and decreased tumor formation. Therefore, the selection pressure to amplify 5q in ccRCC is driven, at least partly, by SQSTM1.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cromosomas Humanos Par 5 / Carcinoma de Células Renales / Dosificación de Gen / Proteínas Adaptadoras Transductoras de Señales / Neoplasias Renales Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cromosomas Humanos Par 5 / Carcinoma de Células Renales / Dosificación de Gen / Proteínas Adaptadoras Transductoras de Señales / Neoplasias Renales Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos