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Cited by 846Lung Cancer Treatments and MutationsLung Cancer Research StudiesCancer Genomics and Diagnostics

The DOI matches its Crossref record; 257 of the 260 references it cites were found in a registry or an index.

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

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Gillette, Michael A., Satpathy, Shankha, Cao, Song, Dhanasekaran, Saravana M., Vasaikar, Suhas V., Krug, Karsten, Petralia, Francesca, Li, Yize, Liang, Wen-Wei, Reva, Boris, Krek, Azra, Ji, Jiayi, Song, Xiaoyu, Liu, Wenke, Hong, Runyu, Yao, Lijun, Blumenberg, Lili, Savage, Sara R., Wendl, Michael C., Wen, Bo, Li, Kai, Tang, Lauren C., MacMullan, Melanie A., Avanessian, Shayan C., Kane, M. Harry, Newton, Chelsea J., Cornwell, MacIntosh, Kothadia, Ramani B., Ma, Weiping, Yoo, Seungyeul, Mannan, Rahul, Vats, Pankaj, Kumar-Sinha, Chandan, Kawaler, Emily A., Omelchenko, Tatiana, Colaprico, Antonio, Geffen, Yifat, Maruvka, Yosef E., da Veiga Leprevost, Felipe, Wiznerowicz, Maciej, Gümüş, Zeynep H., Veluswamy, Rajwanth R., Hostetter, Galen, Heiman, David I., Wyczalkowski, Matthew A., Hiltke, Tara, Mesri, Mehdi, Kinsinger, Christopher R., Boja, Emily S., Omenn, Gilbert S., Chinnaiyan, Arul M., Rodriguez, Henry, Li, Qing Kay, Jewell, Scott D., Thiagarajan, Mathangi, Getz, Gad, Zhang, Bing, Fenyö, David, Ruggles, Kelly V., Cieslik, Marcin P., Robles, Ana I., Clauser, Karl R., Govindan, Ramaswamy, Wang, Pei, Nesvizhskii, Alexey I., Ding, Li, Mani, D.R., Carr, Steven A., Webster, Alex, Francis, Alicia, Charamut, Alyssa, Paulovich, Amanda G., Perou, Amy M., Godwin, Andrew K., Karnuta, Andrii, Marrero-Oliveras, Annette, Hindenach, Barbara, Pruetz, Barbara, Kubisa, Bartosz, Druker, Brian J., Birger, Chet, Jones, Corbin D., Valley, Dana R., Rohrer, Daniel C., Zhou, Daniel Cui, Chan, Daniel W., Chesla, David, Clark, David J., Rykunov, Dmitry, Tan, Donghui, Ponomareva, Elena V., Duffy, Elizabeth, Burks, Eric J., Schadt, Eric E., Bergstrom, Erik J., Fedorov, Eugene S., Malc, Ewa, Wilson, George D., Chen, Hai-Quan, Krzystek, Halina M., Liu, Hongwei, Culpepper, Houston, Sun, Hua, Zhang, Hui, Day, Jacob, Suh, James, Whiteaker, Jeffrey R., Eschbacher, Jennifer, McGee, John, Ketchum, Karen A., Rodland, Karin D., Robinson, Karna, Hoadley, Katherine A., Suzuki, Kei, Um, Ki Sung, Elburn, Kim, Wang, Liang-Bo, Chen, Lijun, Hannick, Linda, Qi, Liqun, Sokoll, Lori J., Wojtyś, Małgorzata, Domagalski, Marcin J., Gritsenko, Marina A., Beasley, Mary B., Monroe, Matthew E., Ellis, Matthew J., Dyer, Maureen, Burke, Meghan C., Borucki, Melissa, Sun, Meng-Hong, Roehrl, Michael H., Birrer, Michael J., Noble, Michael, Schnaubelt, Michael, Vernon, Michael, Chaikin, Michelle, Krotevich, Mikhail, Khan, Munziba, Selvan, Myvizhi Esai, Roche, Nancy, Edwards, Nathan J., Vatanian, Negin, Potapova, Olga, Grady, Pamela, McGarvey, Peter B., Mieczkowski, Piotr, Hariharan, Pushpa, Madan, Rashna, Thangudu, Ratna R., Smith, Richard D., Welsh, Robert J., Zelt, Robert, Mehra, Rohit, Matteotti, Ronald, Mareedu, Sailaja, Payne, Samuel H., Cottingham, Sandra, Markey, Sanford P., Chugh, Seema, Smith, Shaleigh, Tsang, Shirley, Cai, Shuang, Boca, Simina M., Carter, Sonya, Gabriel, Stacey, De Young, Stephanie, Stein, Stephen E., Shankar, Sunita, Krubit, Tanya, Liu, Tao, Skelly, Tara, Bauer, Thomas, Velvulou, Uma, Ozbek, Umut, Petyuk, Vladislav A., Sovenko, Volodymyr, Bocik, William E., Maggio, William W., Chen, Xi, Shi, Yan, Wu, Yige, Hu, Yingwei, Liao, Yuxing, Zhang, Zhen, Shi, Zhiao·2020·Cell
DOI 10.1016/j.cell.2020.06.013PMC PMC7373300
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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.

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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., Webster, A., Francis, A., Charamut, A., Paulovich, A. G., Perou, A. M., Godwin, A. K., Karnuta, A., Marrero-Oliveras, A., Hindenach, B., Pruetz, B., Kubisa, B., Druker, B. J., Birger, C., Jones, C. D., Valley, D. R., Rohrer, D. C., Zhou, D. C., Chan, D. W., Chesla, D., Clark, D. J., Rykunov, D., Tan, D., Ponomareva, E. V., Duffy, E., Burks, E. J., Schadt, E. E., Bergstrom, E. J., Fedorov, E. S., Malc, E., Wilson, G. D., Chen, H.-Q., Krzystek, H. M., Liu, H., Culpepper, H., Sun, H., Zhang, H., Day, J., Suh, J., Whiteaker, J. R., Eschbacher, J., McGee, J., Ketchum, K. A., Rodland, K. D., Robinson, K., Hoadley, K. A., Suzuki, K., Um, K. S., Elburn, K., Wang, L.-B., Chen, L., Hannick, L., Qi, L., Sokoll, L. J., Wojtyś, M., Domagalski, M. J., Gritsenko, M. A., Beasley, M. B., Monroe, M. E., Ellis, M. J., Dyer, M., Burke, M. C., Borucki, M., Sun, M.-H., Roehrl, M. H., Birrer, M. J., Noble, M., Schnaubelt, M., Vernon, M., Chaikin, M., Krotevich, M., Khan, M., Selvan, M. E., Roche, N., Edwards, N. J., Vatanian, N., Potapova, O., Grady, P., McGarvey, P. B., Mieczkowski, P., Hariharan, P., Madan, R., Thangudu, R. R., Smith, R. D., Welsh, R. J., Zelt, R., Mehra, R., Matteotti, R., Mareedu, S., Payne, S. H., Cottingham, S., Markey, S. P., Chugh, S., Smith, S., Tsang, S., Cai, S., Boca, S. M., Carter, S., Gabriel, S., De Young, S., Stein, S. E., Shankar, S., Krubit, T., Liu, T., Skelly, T., Bauer, T., Velvulou, U., Ozbek, U., Petyuk, V. A., Sovenko, V., Bocik, W. E., Maggio, W. W., Chen, X., Shi, Y., Wu, Y., Hu, Y., Liao, Y., Zhang, Z., & Shi, Z.
Affiliations
  • Broad Institute (US)
  • Washington University in St. Louis (US)
  • University of Michigan (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Tisch Cancer Institute (US)
  • New York University (US)
  • Baylor College of Medicine (US)
  • Van Andel Institute (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Miami (US)
  • Poznan University of Medical Sciences (PL)
  • National Cancer Institute (US)
  • Johns Hopkins University (US)
  • Frederick National Laboratory for Cancer Research (US)
Corresponding author
  • Gillette, Michael A.
  • Satpathy, Shankha
  • Carr, Steven A.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2020-07
Volume
182
Issue
1
Pages
200-225.e35
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2020.06.013
PMC
PMC7373300
OpenAlex
W3041397352
Cited by
820
References
260
Citations by year
2026: 129 · 2025: 148 · 2024: 143 · 2023: 151 · 2022: 119 · 2021: 112 · 2020: 15
FWCI
58.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
lung adenocarcinoma, proteogenomics, therapeutic vulnerabilities, KRAS, EGFR, anaplastic lymphoma kinase, STK11, neutrophil degranulation, smoking, field effect, copy number alterations, somatic mutations, protein expression signatures, multi-omics clustering
MeSH terms
Proteogenomics, Adenocarcinoma of Lung, Adult, Aged, Aged, 80 and over, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Phenotype, Phosphoproteins, Biomarkers, Tumor, Oncogene Proteins, Fusion, DNA Methylation, Proteome, DNA Copy Number Variations, Carcinogenesis

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