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Cell DOI:10.1016/j.cell.2020.06.013

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.

Publication TypeJournal Article
Year of Publication2020
AuthorsGillette, MA, Satpathy, S, Cao, S, Dhanasekaran, SM, Vasaikar, SV, Krug, K, Petralia, F, Li, Y, Liang, W-W, Reva, B, Krek, A, Ji, J, Song, X, Liu, W, Hong, R, Yao, L, Blumenberg, L, Savage, SR, Wendl, MC, Wen, B, Li, K, Tang, LC, MacMullan, MA, Avanessian, SC, M Kane, H, Newton, CJ, Cornwell, MI, Kothadia, RB, Ma, W, Yoo, S, Mannan, R, Vats, P, Kumar-Sinha, C, Kawaler, EA, Omelchenko, T, Colaprico, A, Geffen, Y, Maruvka, YE, Leprevost, Fda Veiga, Wiznerowicz, M, Gümüş, ZH, Veluswamy, RR, Hostetter, G, Heiman, DI, Wyczalkowski, MA, Hiltke, T, Mesri, M, Kinsinger, CR, Boja, ES, Omenn, GS, Chinnaiyan, AM, Rodriguez, H, Li, QKay, Jewell, SD, Thiagarajan, M, Getz, G, Zhang, B, Fenyö, D, Ruggles, KV, Cieslik, MP, Robles, AI, Clauser, KR, Govindan, R, Wang, P, Nesvizhskii, AI, Ding, L, Mani, DR, Carr, SA
Corporate AuthorsClinical Proteomic Tumor Analysis Consortium
JournalCell
Volume182
Issue1
Pages200-225.e35
Date Published2020 07 09
ISSN1097-4172
KeywordsAdenocarcinoma of Lung, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinogenesis, DNA Copy Number Variations, DNA Methylation, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Oncogene Proteins, Fusion, Phenotype, Phosphoproteins, Proteogenomics, Proteome
Abstract

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

DOI10.1016/j.cell.2020.06.013
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/32649874?dopt=Abstract

Alternate JournalCell
PubMed ID32649874
PubMed Central IDPMC7373300
Grant ListU24 CA210954 / CA / NCI NIH HHS / United States
U24 CA210967 / CA / NCI NIH HHS / United States
U24 CA210986 / CA / NCI NIH HHS / United States
U24 CA210972 / CA / NCI NIH HHS / United States
P20 GM130423 / GM / NIGMS NIH HHS / United States
P30 ES017885 / ES / NIEHS 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