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

被引：185

作者：

Huang, Chen ^{[1
,2
]}

Chen, Lijun ^{[3
]}

Savage, Sara R. ^{[1
,2
]}

Eguez, Rodrigo Vargas ^{[3
]}

Dou, Yongchao ^{[1
,2
]}

Li, Yize ^{[4
,5
]}

Leprevost, Felipe da Veiga ^{[6
]}

Jaehnig, Eric J. ^{[1
,2
]}

Lei, Jonathan T. ^{[1
,2
]}

Wen, Bo ^{[1
,2
]}

Schnaubelt, Michael ^{[3
]}

Krug, Karsten ^{[7
]}

Song, Xiaoyu ^{[8
,9
]}

Cieslik, Marcin ^{[6
,10
,11
]}

Chang, Hui-Yin ^{[6
]}

Wyczalkowski, Matthew A. ^{[4
,5
]}

Li, Kai ^{[1
,2
]}

Colaprico, Antonio ^{[12
,13
]}

Li, Qing Kay ^{[3
]}

Clark, David J. ^{[3
]}

Hu, Yingwei ^{[3
]}

Cao, Liwei ^{[3
]}

Pan, Jianbo ^{[3
,14
]}

Wang, Yuefan ^{[3
]}

Cho, Kyung-Cho ^{[3
]}

Shi, Zhiao ^{[1
,2
]}

Liao, Yuxing ^{[1
,2
]}

Jiang, Wen ^{[1
,2
]}

Anurag, Meenakshi ^{[1
]}

Ji, Jiayi ^{[8
,9
]}

Yoo, Seungyeul ^{[15
,16
]}

Zhou, Daniel Cui ^{[4
,5
]}

Liang, Wen-Wei ^{[4
,5
]}

Wendl, Michael ^{[4
,5
]}

Vats, Pankaj ^{[11
]}

Carr, Steven A. ^{[7
]}

Mani, D. R. ^{[7
]}

Zhang, Zhen ^{[3
]}

Qian, Jiang ^{[14
]}

Chen, Xi S. ^{[12
,13
]}

Pico, Alexander R. ^{[17
]}

Wang, Pei ^{[15
,16
]}

Chinnaiyan, Arul M. ^{[6
,10
,11
]}

Ketchum, Karen A. ^{[18
]}

Kinsinger, Christopher R. ^{[19
]}

Robles, Ana, I ^{[19
]}

An, Eunkyung ^{[19
]}

Hiltke, Tara ^{[19
]}

Mesri, Mehdi ^{[19
]}

Thiagarajan, Mathangi ^{[20
]}

机构：

[1] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[3] Johns Hopkins Univ, Dept Pathol & Oncol, Baltimore, MD 21231 USA

[4] Washington Univ, Dept Med, St Louis, MO 63110 USA

[5] Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA

[6] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[7] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[8] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[9] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA

[10] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[11] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[12] Univ Miami, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL 33136 USA

[13] Univ Miami, Div Biostat, Dept Publ Hlth Sci, Miller Sch Med, Miami, FL 33136 USA

[14] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD 21231 USA

[15] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[16] Icahn Sch Med Mt Sinai, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA

[17] Gladstone Inst, Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA

[18] ESAC Inc, Rockville, MD 20850 USA

[19] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA

[20] Frederick NaVonal Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21702 USA

[21] Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, Nashville, TN 37232 USA

[22] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA

[23] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-71252 Szczecin, Poland

[24] Int Inst Mol Oncol, PL-60203 Poznan, Poland

[25] Poznan Univ Med Sci, PL-61701 Poznan, Poland

[26] Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland

[27] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA

[28] MD Anderson Canc Ctr, Dept Pathol, Div Pathol & Lab Med, Houston, TX 77030 USA

来源：

CANCER CELL | 2021年 / 39卷 / 03期

关键词：

PLATINUM-BASED CHEMOTHERAPY; PATIENT-DERIVED XENOGRAFTS; FACTOR RECEPTOR ANTIBODY; COPY NUMBER ALTERATION; PHASE-II MULTICENTER; FALSE DISCOVERY RATE; RNA-SEQ DATA; READ ALIGNMENT; OPEN-LABEL; STATISTICAL-MODEL;

D O I：

10.1016/j.ccell.2020.12.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 phospho-sites, 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 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 treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, pro-teogenomics provides a systematic framework to inform HNSCC biology and treatment.

引用

页码：361 / +

页数：35

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