Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma
- David Clark
- Saravana M. Dhanasekaran
- Francesca Petralia
- Jianbo Pan
- Xiaoyu Song
- Yingwei Hu
- Felipe da Veiga Leprevost
- Boris Reva
- T. Mamie Lih
- Hui-Yin Chang
- Weiping Ma
- Chen Huang
- Christopher J. Ricketts
- Lijun Chen
- Azra Krek
- Yize Li
- Dmitry Rykunov
- Qing Kay Li
- Lin S. Chen
- Umut Özbek
- Suhas Vasaikar
- Yige Wu
- Seungyeul Yoo
- Shrabanti Chowdhury
- Matthew A. Wyczalkowski
- Jiayi Ji
- Michael Schnaubelt
- Andy T. Kong
- Sunantha Sethuraman
- Dmitry M. Avtonomov
- Minghui Ao
- Antonio Colaprico
- Song Cao
- Kyung-Cho Cho
- Selim Kalaycı
- Shiyong Ma
- Wenke Liu
- Kelly V. Ruggles
- Anna Calinawan
- Zeynep H. Gümüş
- Daniel Geiszler
- Emily Kawaler
- Guo Ci Teo
- Bo Wen
- Yuping Zhang
- Sarah Keegan
- Kai Li
- Feng Chen
- Nathan Edwards
- Phillip M. Pierorazio
- Xi Chen
- Christian P. Pavlovich
- A. Ari Hakimi
- Gabriel Bromiński
- James J. Hsieh
- Andrzej Antczak
- Tatiana Omelchenko
- Jan Lubiński
- Maciej Wiznerowicz
- W. Marston Linehan
- Christopher R. Kinsinger
- Mathangi Thiagarajan
- Emily S. Boja
- Mehdi Mesri
- Tara Hiltke
- Ana I. Robles
- Henry Rodriguez
- Jiang Qian
- David Fenyö
- Bing Zhang
- Li Ding
- Eric E. Schadt
- Arul M. Chinnaiyan
- Zhen Zhang
- Gilbert S. Omenn
- Marcin Cieślik
- Daniel W. Chan
- Alexey I. Nesvizhskii
- Pei Wang
- Hui Zhang
- A. Samad Hashimi
- Alexander R. Pico
- Alla Y. Karpova
- Alyssa Charamut
- Amanda G. Paulovich
- Amy M. Perou
- Anna Malovannaya
- Annette Marrero-Oliveras
- Anupriya Agarwal
- Barbara Hindenach
- Barbara L. Pruetz
- Beom‐Jun Kim
- Brian Druker
- Chelsea J. Newton
- Chet Birger
- Corbin D. Jones
- Cristina E. Tognon
- D.R. Mani
- Dana R. Valley
- Daniel C. Rohrer
- RSRichard Smith
- RSRichard Smith
- RSRichard Smith
- RSRichard Smith
Cell · 2019 · Cell Press
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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.