Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.

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2019
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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.
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Authors 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;, ;
Journal Cell
Year 2019
DOI S0092-8674(19)31123-7
URL
Keywords
Proteomics tumor microenvironment proteogenomics phosphoproteomics ccrcc drug targets cptac chromosomal translocation immune infiltration renal carcinoma

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