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Cell DOI:10.1016/j.cell.2021.07.016

A proteogenomic portrait of lung squamous cell carcinoma.

Publication TypeJournal Article
Year of Publication2021
AuthorsSatpathy, S, Krug, K, Beltran, PMJean, Savage, SR, Petralia, F, Kumar-Sinha, C, Dou, Y, Reva, B, M Kane, H, Avanessian, SC, Vasaikar, SV, Krek, A, Lei, JT, Jaehnig, EJ, Omelchenko, T, Geffen, Y, Bergstrom, EJ, Stathias, V, Christianson, KE, Heiman, DI, Cieslik, MP, Cao, S, Song, X, Ji, J, Liu, W, Li, K, Wen, B, Li, Y, Gümüş, ZH, Selvan, MEsai, Soundararajan, R, Visal, TH, Raso, MG, Parra, ERoger, Babur, O, Vats, P, Anand, S, Schraink, T, Cornwell, MI, Rodrigues, FMartins, Zhu, H, Mo, C-K, Zhang, Y, Leprevost, Fda Veiga, Huang, C, Chinnaiyan, AM, Wyczalkowski, MA, Omenn, GS, Newton, CJ, Schurer, S, Ruggles, KV, Fenyö, D, Jewell, SD, Thiagarajan, M, Mesri, M, Rodriguez, H, Mani, SA, Udeshi, ND, Getz, G, Suh, J, Li, QKay, Hostetter, G, Paik, PK, Dhanasekaran, SM, Govindan, R, Ding, L, Robles, AI, Clauser, KR, Nesvizhskii, AI, Wang, P, Carr, SA, Zhang, B, Mani, DR, Gillette, MA
Corporate AuthorsClinical Proteomic Tumor Analysis Consortium
JournalCell
Volume184
Issue16
Pages4348-4371.e40
Date Published2021 Aug 05
ISSN1097-4172
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.

DOI10.1016/j.cell.2021.07.016
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/34358469?dopt=Abstract

Alternate JournalCell
PubMed ID34358469
Grant ListU54 HL127624 / HL / NHLBI NIH HHS / United States
U24 CA210972 / CA / NCI NIH HHS / United States
U24 CA210993 / CA / NCI NIH HHS / United States
U24 CA210979 / CA / NCI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States
T32 CA203690 / CA / NCI NIH HHS / United States