Integrated proteogenomic characterization of clear cell renal cell carcinoma Journal Article
| Authors: | Clark, D. J.; Dhanasekaran, S. M.; Petralia, F.; Pan, J.; Song, X.; Hu, Y.; da Veiga Leprevost, F.; Reva, B.; Lih, T. S. M.; Chang, H. Y.; Ma, W.; Huang, C.; Ricketts, C. J.; Chen, L.; Krek, A.; Li, Y.; Rykunov, D.; Li, Q. K.; Chen, L. S.; Ozbek, U.; Vasaikar, S.; Wu, Y.; Yoo, S.; Chowdhury, S.; Wyczalkowski, M. A.; Ji, J.; Schnaubelt, M.; Kong, A.; Sethuraman, S.; Avtonomov, D. M.; Ao, M.; Colaprico, A.; Cao, S.; Cho, K. C.; Kalayci, S.; Ma, S.; Liu, W.; Ruggles, K.; Calinawan, A.; Gümüş, Z. H.; Geizler, D.; Kawaler, E.; Teo, G. C.; Wen, B.; Zhang, Y.; Keegan, S.; Li, K.; Chen, F.; Edwards, N.; Pierorazio, P. M.; Chen, X. S.; Pavlovich, C. P.; Hakimi, A. A.; Brominski, G.; Hsieh, J. J.; Antczak, A.; Omelchenko, T.; Lubinski, J.; Wiznerowicz, M.; Linehan, W. M.; Kinsinger, C. R.; Thiagarajan, M.; Boja, E. S.; Mesri, M.; Hiltke, T.; Robles, A. I.; Rodriguez, H.; Qian, J.; Fenyö, D.; Zhang, B.; Ding, L.; Schadt, E.; Chinnaiyan, A. M.; Zhang, Z.; Omenn, G. S.; Cieslik, M.; Chan, D. W.; Nesvizhskii, A. I.; Wang, P.; Zhang, H.; Clinical Proteomic Tumor Analysis Consortium |
| Article Title: | Integrated proteogenomic characterization of clear cell renal cell carcinoma |
| Abstract: | Comprehensive proteogenomic characterization in 103 treatment-naive clear cell renal cell carcinoma patient samples highlights tumor-specific alterations at the proteomic level that are unrevealed by transcriptomic profiling and proposes a revised subtyping scheme based on integrated omics analysis. © 2019 Elsevier Inc. 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. © 2019 Elsevier Inc. |
| Keywords: | proteomics; tumor microenvironment; drug targets; chromosomal translocation; renal carcinoma; phosphoproteomics; immune infiltration; ccrcc; proteogenomics; cptac |
| Journal Title: | Cell |
| Volume: | 179 |
| Issue: | 4 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2019-10-31 |
| Start Page: | 964 |
| End Page: | 983.e31 |
| Language: | English |
| DOI: | 10.1016/j.cell.2019.10.007 |
| PROVIDER: | scopus |
| PUBMED: | 31675502 |
| PMCID: | PMC7331093 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
