Your browser doesn't support javascript.
loading
Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma.
Huang, Chen; Chen, Lijun; Savage, Sara R; Eguez, Rodrigo Vargas; Dou, Yongchao; Li, Yize; da Veiga Leprevost, Felipe; Jaehnig, Eric J; Lei, Jonathan T; Wen, Bo; Schnaubelt, Michael; Krug, Karsten; Song, Xiaoyu; Cieslik, Marcin; Chang, Hui-Yin; Wyczalkowski, Matthew A; Li, Kai; Colaprico, Antonio; Li, Qing Kay; Clark, David J; Hu, Yingwei; Cao, Liwei; Pan, Jianbo; Wang, Yuefan; Cho, Kyung-Cho; Shi, Zhiao; Liao, Yuxing; Jiang, Wen; Anurag, Meenakshi; Ji, Jiayi; Yoo, Seungyeul; Zhou, Daniel Cui; Liang, Wen-Wei; Wendl, Michael; Vats, Pankaj; Carr, Steven A; Mani, D R; Zhang, Zhen; Qian, Jiang; Chen, Xi S; Pico, Alexander R; Wang, Pei; Chinnaiyan, Arul M; Ketchum, Karen A; Kinsinger, Christopher R; Robles, Ana I; An, Eunkyung; Hiltke, Tara; Mesri, Mehdi; Thiagarajan, Mathangi.
Affiliation
  • Huang C; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Chen L; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Savage SR; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Eguez RV; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Dou Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • 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.
  • da Veiga Leprevost F; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Jaehnig EJ; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Lei JT; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wen B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Schnaubelt M; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Krug K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Song X; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Cieslik M; 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; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Chang HY; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, 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.
  • Li K; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Colaprico A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Division of Biostatistics, Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Li QK; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Clark DJ; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Hu Y; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Cao L; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Pan J; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Ophthalmology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Wang Y; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Cho KC; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Shi Z; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liao Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Jiang W; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Anurag M; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Ji J; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, 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.
  • Zhou DC; 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.
  • Liang WW; 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 M; 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.
  • Vats P; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Carr SA; 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.
  • Zhang Z; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Qian J; Department of Ophthalmology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Chen XS; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Division of Biostatistics, Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Pico AR; Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA.
  • Wang P; 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.
  • Chinnaiyan AM; 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; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Ketchum KA; ESAC, Inc., Rockville, MD 20850, United States.
  • Kinsinger CR; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Robles AI; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • An E; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Hiltke T; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Mesri M; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Thiagarajan M; Leidos Biomedical Research Inc., Frederick NaVonal Laboratory for Cancer Research, Frederick, MD 21702, USA.
Cancer Cell ; 39(3): 361-379.e16, 2021 03 08.
Article in En | MEDLINE | ID: mdl-33417831
ABSTRACT
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Papillomavirus Infections / Antineoplastic Agents, Immunological / Squamous Cell Carcinoma of Head and Neck Type of study: Prognostic_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2021 Type: Article Affiliation country: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Papillomavirus Infections / Antineoplastic Agents, Immunological / Squamous Cell Carcinoma of Head and Neck Type of study: Prognostic_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2021 Type: Article Affiliation country: United States