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A proteogenomic portrait of lung squamous cell carcinoma.
Satpathy, Shankha; Krug, Karsten; Jean Beltran, Pierre M; Savage, Sara R; Petralia, Francesca; Kumar-Sinha, Chandan; Dou, Yongchao; Reva, Boris; Kane, M Harry; Avanessian, Shayan C; Vasaikar, Suhas V; Krek, Azra; Lei, Jonathan T; Jaehnig, Eric J; Omelchenko, Tatiana; Geffen, Yifat; Bergstrom, Erik J; Stathias, Vasileios; Christianson, Karen E; Heiman, David I; Cieslik, Marcin P; Cao, Song; Song, Xiaoyu; Ji, Jiayi; Liu, Wenke; Li, Kai; Wen, Bo; Li, Yize; Gümüs, Zeynep H; Selvan, Myvizhi Esai; Soundararajan, Rama; Visal, Tanvi H; Raso, Maria G; Parra, Edwin Roger; Babur, Özgün; Vats, Pankaj; Anand, Shankara; Schraink, Tobias; Cornwell, MacIntosh; Rodrigues, Fernanda Martins; Zhu, Houxiang; Mo, Chia-Kuei; Zhang, Yuping; da Veiga Leprevost, Felipe; Huang, Chen; Chinnaiyan, Arul M; Wyczalkowski, Matthew A; Omenn, Gilbert S; Newton, Chelsea J; Schurer, Stephan.
Afiliación
  • Satpathy S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: shankha@broadinstitute.org.
  • Krug K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Jean Beltran PM; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Savage SR; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Petralia F; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kumar-Sinha C; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Dou Y; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Reva B; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kane MH; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Avanessian SC; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Vasaikar SV; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Krek A; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lei JT; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Jaehnig EJ; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Omelchenko T; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Geffen Y; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Bergstrom EJ; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Stathias V; Sylvester Comprehensive Cancer Center and Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
  • Christianson KE; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Heiman DI; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Cieslik MP; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Cao S; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Song X; Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Ji J; Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Liu W; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Li K; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wen B; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Li Y; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Gümüs ZH; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Selvan ME; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Soundararajan R; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Visal TH; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Raso MG; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Parra ER; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Babur Ö; Computer Science Department, University of Massachusetts Boston, Boston, MA 02125, USA.
  • Vats P; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Anand S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Schraink T; Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Cornwell M; Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Rodrigues FM; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Zhu H; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Mo CK; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Zhang Y; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • da Veiga Leprevost F; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Huang C; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Chinnaiyan AM; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Wyczalkowski MA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Omenn GS; 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.
  • Schurer S; Sylvester Comprehensive Cancer Center and Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Cell ; 184(16): 4348-4371.e40, 2021 08 05.
Article en En | MEDLINE | ID: mdl-34358469
ABSTRACT
Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Proteogenómica / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Proteogenómica / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article