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Cancer Cell DOI:10.1016/j.ccell.2020.12.007

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

Publication TypeJournal Article
Year of Publication2021
AuthorsHuang, C, Chen, L, Savage, SR, Eguez, RVargas, Dou, Y, Li, Y, Leprevost, Fda Veiga, Jaehnig, EJ, Lei, JT, Wen, B, Schnaubelt, M, Krug, K, Song, X, Cieślik, M, Chang, H-Y, Wyczalkowski, MA, Li, K, Colaprico, A, Li, QKay, Clark, DJ, Hu, Y, Cao, L, Pan, J, Wang, Y, Cho, K-C, Shi, Z, Liao, Y, Jiang, W, Anurag, M, Ji, J, Yoo, S, Zhou, DCui, Liang, W-W, Wendl, M, Vats, P, Carr, SA, Mani, DR, Zhang, Z, Qian, J, Chen, XS, Pico, AR, Wang, P, Chinnaiyan, AM, Ketchum, KA, Kinsinger, CR, Robles, AI, An, E, Hiltke, T, Mesri, M, Thiagarajan, M, Weaver, AM, Sikora, AG, Lubinski, J, Wierzbicka, M, Wiznerowicz, M, Satpathy, S, Gillette, MA, Miles, G, Ellis, MJ, Omenn, GS, Rodriguez, H, Boja, ES, Dhanasekaran, SM, Ding, L, Nesvizhskii, AI, El-Naggar, AK, Chan, DW, Zhang, H, Zhang, B
Corporate AuthorsClinical Proteomic Tumor Analysis Consortium
JournalCancer Cell
Date Published2021 Jan 07
ISSN1878-3686
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.

DOI10.1016/j.ccell.2020.12.007
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/33417831?dopt=Abstract

Alternate JournalCancer Cell
PubMed ID33417831