Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

被引：273

作者：

Clark, David J. ^{[1
]}

Dhanasekaran, Saravana M. ^{[2
]}

Petralia, Francesca ^{[3
,4
]}

Pan, Jianbo ^{[1
]}

Song, Xiaoyu ^{[5
,6
]}

Hu, Yingwei ^{[1
]}

Leprevost, Felipe da Veiga ^{[2
]}

Reva, Boris ^{[3
,4
]}

Lih, Tung-Shing M. ^{[1
]}

Chang, Hui-Yin ^{[2
]}

Ma, Weiping ^{[3
,4
]}

Huang, Chen ^{[7
]}

Ricketts, Christopher J. ^{[8
]}

Chen, Lijun ^{[1
]}

Krek, Azra ^{[3
,4
]}

Li, Yize ^{[9
]}

Rykunov, Dmitry ^{[3
,4
]}

Li, Qing Kay ^{[1
]}

Chen, Lin S. ^{[10
]}

Ozbek, Umut ^{[5
,6
]}

Vasaikar, Suhas ^{[11
]}

Wu, Yige ^{[9
]}

Yoo, Seungyeul ^{[3
,4
]}

Chowdhury, Shrabanti ^{[3
,4
]}

Wyczalkowski, Matthew A. ^{[9
]}

Ji, Jiayi ^{[5
,6
]}

Schnaubelt, Michael ^{[1
]}

Kong, Andy ^{[2
]}

Sethuraman, Sunantha ^{[9
]}

Avtonomov, Dmitry M. ^{[2
]}

Ao, Minghui ^{[1
]}

Colaprico, Antonio ^{[12
]}

Cao, Song ^{[9
]}

Cho, Kyung-Cho ^{[1
]}

Kalayci, Selim ^{[3
,4
]}

Ma, Shiyong ^{[1
]}

Liu, Wenke ^{[13
,14
]}

Ruggles, Kelly ^{[15
]}

Calinawan, Anna ^{[3
,4
]}

Gumus, Zeynep H. ^{[3
,4
]}

Geizler, Daniel ^{[16
]}

Kawaler, Emily ^{[13
,14
]}

Teo, Guo Ci ^{[2
]}

Wen, Bo ^{[7
]}

Zhang, Yuping ^{[2
]}

Keegan, Sarah ^{[13
,14
]}

Li, Kai ^{[7
]}

Chen, Feng ^{[17
,18
]}

Edwards, Nathan ^{[19
]}

Pierorazio, Phillip M. ^{[20
,21
]}

机构：

[1] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA

[2] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[3] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[7] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA

[8] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[9] Washington Univ, Sch Med, St Louis, MO 63110 USA

[10] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[12] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA

[13] NYU, Sch Med, Inst Syst Genet, New York, NY 10016 USA

[14] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[15] NYU, Sch Med, Dept Med, New York, NY 10016 USA

[16] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[17] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[18] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

[19] Georgetown Univ, Dept Biochem & Cell Biol, Washington, DC 20007 USA

[20] Johns Hopkins Univ, Brady Urol Inst, Baltimore, MD 21231 USA

[21] Johns Hopkins Univ, Dept Urol, Baltimore, MD 21231 USA

[22] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[23] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA

[24] Poznan Univ Med Sci, Dept Urol, Szwajcarska 3, PL-61285 Poznan, Poland

[25] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[26] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, New York, NY 10065 USA

[27] Pomeranian Med Univ, Dept Genet & Pathol, PL-71252 Szczecin, Poland

[28] Int Inst Mol Oncol, PL-60203 Poznan, Poland

[29] Poznan Univ Med Sci, PL-60701 Poznan, Poland

[30] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA

[31] Frederick Natl Lab Canc Res, Frederick, MD 21702 USA

[32] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD 21231 USA

[33] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[34] Sema4, Stamford, CT 06902 USA

[35] Univ Michigan, Dept Internal Med, Human Genet, Ann Arbor, MI 48109 USA

[36] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA

来源：

CELL | 2019年 / 179卷 / 04期

关键词：

COMPREHENSIVE MOLECULAR CHARACTERIZATION; HYPOXIA-INDUCIBLE FACTORS; SET ENRICHMENT ANALYSIS; COPY NUMBER ALTERATION; FALSE DISCOVERY RATE; C-MYC; SIGNALING PATHWAYS; TUMOR-SUPPRESSOR; RIBOSOME BIOGENESIS; STATISTICAL-MODEL;

D O I：

10.1016/j.cell.2019.10.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：964 / +

页数：51

共 188 条

[1] From big data analysis to personalized medicine for all: challenges and opportunities [J].

Alyass, Akram ;

Turcotte, Michelle ;

Meyre, David .

BMC MEDICAL GENOMICS, 2015, 8

[2] Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies [J].

Anderson, Kristin G. ;

Stromnes, Ingunn M. ;

Greenberg, Philip D. .

CANCER CELL, 2017, 31 (03) :311-325

[3]

[Anonymous], BIORXIV

[4]

[Anonymous], 2016, NUCLEIC ACIDS RES, DOI DOI 10.1093/NAR/GKW550

[5]

[Anonymous], J CLIN ONCOL

[6]

[Anonymous], MOL CELL PROTEOMI S1

[7]

[Anonymous], STAT SYST BIOL

[8]

[Anonymous], 2016, F1000RESEARCH

[9]

[Anonymous], J IMMUN RES

[10]

[Anonymous], NEW ENGL J MED

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