Proteogenomic characterization reveals therapeutic vulnerabilities in lung adenocarcinoma

By Michael A. Gillette, S. Satpathy, Song Cao, S. Dhanasekaran, S. Vasaikar, Karsten Krug, F. Petralia, Y. Li, Wen-Wei Liang, B. Reva and 15 more. Cell, 2020

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Summary 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.

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/24271741d5c46e3a2d3719a71e68311e7c122b0a