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Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

  1. Author:
    Huang, Chen
    Chen, Lijun
    Savage, Sara R.
    Eguez, Rodrigo Vargas
    Dou, Yongchao
    Li, Yize
    Leprevost, Felipe da Veiga
    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
    An, Eunkyung
    Hiltke, Tara
    Mesri, Mehdi
    Thiagarajan,Mathangi
    Weaver, Alissa M.
    Sikora, Andrew G.
    Lubinski, Jan
    Wierzbicka, Malgorzata
    Wiznerowicz, Maciej
    Satpathy, Shankha
    Gillette, Michael A.
    Miles, George
    Ellis, Matthew J.
    Omenn, Gilbert S.
    Rodriguez, Henry
    Boja, Emily S.
    Dhanasekaran, Saravana M.
    Ding, Li
    Nesvizhskii, Alexey
    El-Naggar, Adel K.
    Chan, Daniel W.
    Zhang, Hui
    Zhang, Bing

  2. Author Address

    Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.Johns Hopkins Univ, Dept Pathol & Oncol, Baltimore, MD 21231 USA.Washington Univ, Dept Med, St Louis, MO 63110 USA.Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.Univ Miami, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL 33136 USA.Univ Miami, Div Biostat, Dept Publ Hlth Sci, Miller Sch Med, Miami, FL 33136 USA.Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD 21231 USA.Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.Icahn Sch Med Mt Sinai, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA.Gladstone Inst, Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA.ESAC Inc, Rockville, MD 20850 USA.NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA.Frederick NaVonal Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21702 USA.Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, Nashville, TN 37232 USA.Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-71252 Szczecin, Poland.Int Inst Mol Oncol, PL-60203 Poznan, Poland.Poznan Univ Med Sci, PL-61701 Poznan, Poland.Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland.Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.MD Anderson Canc Ctr, Dept Pathol, Div Pathol & Lab Med, Houston, TX 77030 USA.
    1. Year: 2021
    2. Date: Mar 8
    3. Epub Date: 2021 Jan 07
  2. Journal: Cancer Cell
  3. Cell Press
    1. 39
    2. 3
    3. Pages: 361-379
  5. Type of Article: Article
  6. ISSN: 1535-6108
  1. Abstract:

    Wepresent 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 phospho-sites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation ofmutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dys-regulated 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 mono-therapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatmentwith CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, pro-teogenomics provides a systematic framework to inform HNSCC biology and treatment.

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  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2020.12.007
  3. PMID: 33417831
  4. PMCID: PMC7946781
  5. View record in Web of Science®
  6. WOS: 000627120300011

Library Notes

  1. Open Access Publication
  2. Fiscal Year: FY2020-2021
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