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Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness.
Li, Yize; Lih, Tung-Shing M; Dhanasekaran, Saravana M; Mannan, Rahul; Chen, Lijun; Cieslik, Marcin; Wu, Yige; Lu, Rita Jiu-Hsien; Clark, David J; Kolodziejczak, Iga; Hong, Runyu; Chen, Siqi; Zhao, Yanyan; Chugh, Seema; Caravan, Wagma; Naser Al Deen, Nataly; Hosseini, Noshad; Newton, Chelsea J; Krug, Karsten; Xu, Yuanwei; Cho, Kyung-Cho; Hu, Yingwei; Zhang, Yuping; Kumar-Sinha, Chandan; Ma, Weiping; Calinawan, Anna; Wyczalkowski, Matthew A; Wendl, Michael C; Wang, Yuefan; Guo, Shenghao; Zhang, Cissy; Le, Anne; Dagar, Aniket; Hopkins, Alex; Cho, Hanbyul; Leprevost, Felipe da Veiga; Jing, Xiaojun; Teo, Guo Ci; Liu, Wenke; Reimers, Melissa A; Pachynski, Russell; Lazar, Alexander J; Chinnaiyan, Arul M; Van Tine, Brian A; Zhang, Bing; Rodland, Karin D; Getz, Gad; Mani, D R; Wang, Pei; Chen, Feng.
Afiliação
  • Li Y; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Lih TM; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Dhanasekaran SM; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: saravana@med.umich.edu.
  • Mannan R; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Chen L; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Cieslik M; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Wu Y; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Lu RJ; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Clark DJ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Kolodziejczak I; International Institute for Molecular Oncology, 60-203 Poznan, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.
  • Hong R; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Chen S; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Zhao Y; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Chugh S; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Caravan W; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Naser Al Deen N; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Hosseini N; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Newton CJ; Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  • Krug K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Xu Y; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
  • Cho KC; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Hu Y; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Zhang Y; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kumar-Sinha C; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Ma W; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Calinawan A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Wyczalkowski MA; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Wendl MC; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Wang Y; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Guo S; Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
  • Zhang C; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
  • Le A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University School of Medicine,
  • Dagar A; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Hopkins A; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Cho H; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Leprevost FDV; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Jing X; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Teo GC; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Liu W; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Reimers MA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
  • Pachynski R; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
  • Lazar AJ; Departments of Pathology and Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chinnaiyan AM; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Van Tine BA; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Zhang B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Rodland KD; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Getz G; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Mani DR; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Wang P; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Chen F; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Cancer Cell ; 41(1): 139-163.e17, 2023 01 09.
Article em En | MEDLINE | ID: mdl-36563681
ABSTRACT
Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Proteogenômica / Neoplasias Renais Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Proteogenômica / Neoplasias Renais Idioma: En Ano de publicação: 2023 Tipo de documento: Article