Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma | Zendy

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Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

Author(s) -

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 Steven 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 Karpova,

Alyssa Charamut,

Amanda G. Paulovich,

Amy M. Perou,

Anna Malovannaya,

Annette Marrero-Oliveras,

Anupriya Agarwal,

Barbara Hindenach,

Barbara L. Pruetz,

BeomJun Kim,

Brian J. Druker,

Chelsea J. Newton,

Chet Birger,

Corbin D. Jones,

Cristina E. Tog,

D.R. Mani,

Dana R. Valley,

Daniel C. Rohrer,

Daniel Cui Zhou,

Darlene Tansil,

David Chesla,

David I. Heiman,

David A. Wheeler,

Donghui Tan,

Doug W. Chan,

Emek Demir,

Ewa P. Malc,

Francesmary Modugno,

Gaddy Getz,

Galen Hostetter,

George D. Wilson,

Gerald W. Hart,

Heng Zhu,

Hongwei Liu,

Houston Culpepper,

Hua Sun,

Hua Zhou,

Jacob Day,

James Suh,

Jasmine Huang,

Jason McDermott,

Jeffrey R. Whiteaker,

Jeffrey W. Tyner,

Jennifer Eschbacher,

Jin Chen,

John P. McGee,

Jun Zhu,

Karen A. Ketchum,

Karin Rodland,

Karl R. Clauser,

Karna Robinson,

Karsten Krug,

Katherine A. Hoadley,

Ki Sung Um,

Kim Elburn,

Kimberly Holloway,

Liang-Bo Wang,

Lili M. Blumenberg,

Linda I. Hannick,

Liqun Qi,

Lori J. Sokoll,

MacIntosh Cornwell,

Marc Loriaux,

Marcin J. Domagalski,

Marina Gritsenko,

Matthew L. Anderson,

Matthew Monroe,

Matthew J. Ellis,

Maureen A. Dyer,

Meenakshi Anurag,

Meghan C. Burke,

Melissa Borucki,

Michael A. Gillette,

Michael J. Birrer,

Michael R. Lewis,

Michael Ittmann,

Michael J. Smith,

Michael W. Ver,

Michelle Chaikin,

Milan G. Chheda,

Munziba Khan,

Nancy Roche,

Negin Vatanian,

Nicole Tignor,

Noam D. Beckmann,

Pamela Grady,

Patricia Castro,

Paul Piehowski,

Peter B. McGarvey,

Piotr A. Mieczkowski,

Pushpa Hariharan,

Qingsong Gao,

Rajiv Dhir,

Ramani Kothadia,

Ratna R. Thangudu,

Rebecca Montgomery,

Reyka G. Jayasinghe,

Richard Smith,

Robert A. Edwards,

Robert Zelt,

Ross M. Bremner,

Ruiyang Liu,

Runyu Hong,

Sailaja Mareedu,

Samuel Payne,

Sandra Cottingham,

Sanford P. Markey,

Scott D. Jewell,

Shalin S. Patel,

Shankha Satpathy,

Shan Richey,

Sherri R. Davies,

Shuang Cai,

Simina M. Boca,

Snehal Patil,

Sohini Sengupta,

Sonya Carter,

Stacey Gabriel,

Stefani N. Thomas,

Stephanie Young,

Stephen E. Stein,

Steven A. Carr,

Steven M. Foltz,

S. G. Hilsenbeck,

Tanya Krubit,

Tao Liu,

Tara Skelly,

Thomas F. Westbrook,

Uma Borate,

Uma Velvulou,

Vladislav Petyuk,

William Bocik,

Xi Chen,

Yan Shi,

Yifat Geffen,

Yihao Lu,

Ying Wang,

Yosef E. Maruvka,

Zhi Li,

Zhiao Shi,

Zhidong Tu

Publication year - 2019

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2019.10.007

Subject(s) - biology , renal cell carcinoma , cell , computational biology , proteogenomics , cancer research , microbiology and biotechnology , genetics , pathology , gene , genomics , genome , medicine

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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