Proteogenomic characterization reveals therapeutic vulnerabilities in lung adenocarcinoma Journal Article
| Authors: | Gillette, M. A.; Satpathy, S.; Cao, S.; Dhanasekaran, S. M.; Vasaikar, S. V.; 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, S. R.; Wendl, M. C.; Wen, B.; Li, K.; Tang, L. C.; MacMullan, M. A.; Avanessian, S. C.; Kane, M. H.; Newton, C. J.; Cornwell, M.; Kothadia, R. B.; Ma, W.; Yoo, S.; Mannan, R.; Vats, P.; Kumar-Sinha, C.; Kawaler, E. A.; Omelchenko, T.; Colaprico, A.; Geffen, Y.; Maruvka, Y. E.; da Veiga Leprevost, F.; Wiznerowicz, M.; Gümüş, Z. H.; Veluswamy, R. R.; Hostetter, G.; Heiman, D. I.; Wyczalkowski, M. A.; Hiltke, T.; Mesri, M.; Kinsinger, C. R.; Boja, E. S.; Omenn, G. S.; Chinnaiyan, A. M.; Rodriguez, H.; Li, Q. K.; Jewell, S. D.; Thiagarajan, M.; Getz, G.; Zhang, B.; Fenyö, D.; Ruggles, K. V.; Cieslik, M. P.; Robles, A. I.; Clauser, K. R.; Govindan, R.; Wang, P.; Nesvizhskii, A. I.; Ding, L.; Mani, D. R.; Carr, S. A.; Clinical Proteomic Tumor Analysis Consortium |
| Article Title: | Proteogenomic characterization reveals therapeutic vulnerabilities in lung adenocarcinoma |
| 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. © 2020 Elsevier Inc. Comprehensive proteogenomic characterization of lung adenocarcinomas and paired normal adjacent tissues from patients of diverse smoking status and country of origin yields insights into cancer taxonomy, oncogenesis, and immune response; offers novel candidate biomarkers and therapeutic targets; and provides a community resource for further discovery. © 2020 Elsevier Inc. |
| Keywords: | adult; controlled study; human tissue; protein expression; aged; gene mutation; major clinical study; somatic mutation; adenocarcinoma; mass spectrometry; phenotype; gene; epidermal growth factor receptor; protein; lung cancer; phosphorylation; proteomics; lung adenocarcinoma; immune response; neutrophil; epigenetics; carcinogenicity; gene fusion; genomics; egfr gene; gene dosage; k ras protein; disease predisposition; acetylation; degranulation; kras gene; phosphoproteomics; alk gene; human; male; female; priority journal; article; proteogenomics; cptac |
| Journal Title: | Cell |
| Volume: | 182 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2020-07-09 |
| Start Page: | 200 |
| End Page: | 225.e35 |
| Language: | English |
| DOI: | 10.1016/j.cell.2020.06.013 |
| PUBMED: | 32649874 |
| PROVIDER: | scopus |
| PMCID: | PMC7373300 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
