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Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.
Clark, David J; Dhanasekaran, Saravana M; Petralia, Francesca; Pan, Jianbo; Song, Xiaoyu; Hu, Yingwei; da Veiga Leprevost, Felipe; Reva, Boris; Lih, Tung-Shing M; Chang, Hui-Yin; Ma, Weiping; Huang, Chen; Ricketts, Christopher J; Chen, Lijun; Krek, Azra; Li, Yize; Rykunov, Dmitry; Li, Qing Kay; Chen, Lin S; Ozbek, Umut; Vasaikar, Suhas; Wu, Yige; Yoo, Seungyeul; Chowdhury, Shrabanti; Wyczalkowski, Matthew A; Ji, Jiayi; Schnaubelt, Michael; Kong, Andy; Sethuraman, Sunantha; Avtonomov, Dmitry M; Ao, Minghui; Colaprico, Antonio; Cao, Song; Cho, Kyung-Cho; Kalayci, Selim; Ma, Shiyong; Liu, Wenke; Ruggles, Kelly; Calinawan, Anna; Gümüs, Zeynep H; Geiszler, Daniel; Kawaler, Emily; Teo, Guo Ci; Wen, Bo; Zhang, Yuping; Keegan, Sarah; Li, Kai; Chen, Feng; Edwards, Nathan; Pierorazio, Phillip M.
Affiliation
  • Clark DJ; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Dhanasekaran SM; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Petralia F; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Pan J; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Song X; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hu Y; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • da Veiga Leprevost F; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Reva B; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lih TM; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Chang HY; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Ma W; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Huang C; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Ricketts CJ; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen L; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Krek A; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Li Y; Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Rykunov D; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Li QK; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Chen LS; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA.
  • Ozbek U; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Vasaikar S; Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wu Y; Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Yoo S; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Chowdhury S; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Wyczalkowski MA; Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Ji J; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Schnaubelt M; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Kong A; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Sethuraman S; Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Avtonomov DM; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Ao M; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Colaprico A; Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Cao S; Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Cho KC; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Kalayci S; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Ma S; Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Liu W; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • Ruggles K; Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
  • Calinawan A; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Gümüs ZH; Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Geiszler D; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kawaler E; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • Teo GC; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Wen B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Zhang Y; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Keegan S; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • Li K; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Chen F; Departments of Medicine and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Edwards N; Department of Biochemistry and Cellular Biology, Georgetown University, Washington, DC 20007, USA.
  • Pierorazio PM; Brady Urological Institute and Department of Urology, Johns Hopkins University, Baltimore, MD 21231, USA.
Cell ; 179(4): 964-983.e31, 2019 10 31.
Article in En | MEDLINE | ID: mdl-31675502
ABSTRACT
To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Renal Cell / Transcriptome / Proteogenomics / Neoplasm Proteins Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2019 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Renal Cell / Transcriptome / Proteogenomics / Neoplasm Proteins Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2019 Type: Article Affiliation country: United States