Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.
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Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.

Clark, David J;Dhanasekaran, Saravana M;Petralia, Francesca;Pan, Jianbo;Song, Xiaoyu;Hu, Yingwei;da Veiga Leprevost, Felipe;Reva, Boris;Lih, Tung-Shing M;Chang, Hui-Yin;Ma, Weiping;Huang, Chen;Ricketts, Christopher J;Chen, Lijun;Krek, Azra;Li, Yize;Rykunov, Dmitry;Li, Qing Kay;Chen, Lin S;Ozbek, Umut;Vasaikar, Suhas;Wu, Yige;Yoo, Seungyeul;Chowdhury, Shrabanti;Wyczalkowski, Matthew A;Ji, Jiayi;Schnaubelt, Michael;Kong, Andy;Sethuraman, Sunantha;Avtonomov, Dmitry M;Ao, Minghui;Colaprico, Antonio;Cao, Song;Cho, Kyung-Cho;Kalayci, Selim;Ma, Shiyong;Liu, Wenke;Ruggles, Kelly;Calinawan, Anna;Gümüş, Zeynep H;Geizler, Daniel;Kawaler, Emily;Teo, Guo Ci;Wen, Bo;Zhang, Yuping;Keegan, Sarah;Li, Kai;Chen, Feng;Edwards, Nathan;Pierorazio, Phillip M;Chen, Xi Steven;Pavlovich, Christian P;Hakimi, A Ari;Brominski, Gabriel;Hsieh, James J;Antczak, Andrzej;Omelchenko, Tatiana;Lubinski, Jan;Wiznerowicz, Maciej;Linehan, W Marston;Kinsinger, Christopher R;Thiagarajan, Mathangi;Boja, Emily S;Mesri, Mehdi;Hiltke, Tara;Robles, Ana I;Rodriguez, Henry;Qian, Jiang;Fenyö, David;Zhang, Bing;Ding, Li;Schadt, Eric;Chinnaiyan, Arul M;Zhang, Zhen;Omenn, Gilbert S;Cieslik, Marcin;Chan, Daniel W;Nesvizhskii, Alexey I;Wang, Pei;Zhang, Hui;, ;
Cell 2019 Vol. 179 pp. 964-983.e31
382
clark2019integratedcell

Abstract

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.

Keywords

Proteomics tumor microenvironment proteogenomics phosphoproteomics ccrcc drug targets cptac chromosomal translocation immune infiltration renal carcinoma

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S0092-8674(19)31123-7

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