Pan-cancer proteogenomics connects oncogenic drivers to functional states

Clinical Proteomic Tumor Analysis Consortium; Yize Li; Eduard Porta-Pardo; Collin Tokheim; Matthew H. Bailey; Tomer M. Yaron; Vasileios Stathias; Yifat Geffen; Kathleen J. Imbach; Song Cao; Shankara Anand; Yo Akiyama; Wenke Liu; Matthew A. Wyczalkowski; Yizhe Song; Erik P. Storrs; Michael C. Wendl; Wubing Zhang; Mustafa Sibai; Victoria Ruiz-Serra; Wen Wei Liang; Nadezhda V. Terekhanova; Fernanda Martins Rodrigues; Karl R. Clauser; David I. Heiman; Qing Zhang; Francois Aguet; Anna P. Calinawan; Saravana M. Dhanasekaran; Chet Birger; Shankha Satpathy; Daniel Cui Zhou; Liang Bo Wang; Jessika Baral; Jared L. Johnson; Emily M. Huntsman; Pietro Pugliese; Antonio Colaprico; Antonio Iavarone; Milan G. Chheda; Christopher J. Ricketts; David Fenyö; Samuel H. Payne; Henry Rodriguez; Ana I. Robles; Michael A. Gillette; Chandan Kumar-Sinha; Alexander J. Lazar; Lewis C. Cantley; Gad Getz; Li Ding; Eunkyung An; Meenakshi Anurag; Jasmin Bavarva; Michael J. Birrer; Anna Calinawan; Michele Ceccarelli; Daniel W. Chan; Arul M. Chinnaiyan; Hanbyul Cho; Shrabanti Chowdhury; Marcin P. Cieslik; Felipe da Veiga Leprevost; Corbin Day; Marcin J. Domagalski; Yongchao Dou; Brian J. Druker; Nathan Edwards; Matthew J. Ellis; Myvizhi Esai Selvan; Steven M. Foltz; Alicia Francis; Tania J. Gonzalez Robles; Sara J.C. Gosline; Zeynep H. Gümüş; Tara Hiltke; Runyu Hong; Galen Hostetter; Yingwei Hu; Chen Huang; Emily Huntsman; Eric J. Jaehnig; Scott D. Jewel; Jiayi Ji; Wen Jiang; Lizabeth Katsnelson; Karen A. Ketchum; Iga Kolodziejczak; Jonathan T. Lei; Yuxing Liao; Caleb M. Lindgren; Tao Liu; Weiping Ma; Wilson McKerrow; Alexey I. Nesvizhskii; Chelsea Newton; Robert Oldroyd; Gilbert S. Omenn; Amanda G. Paulovich; Francesca Petralia; Boris Reva; Karin D. Rodland; Kelly V. Ruggles; Dmitry Rykunov; Sara R. Savage; Eric E. Schadt; Michael Schnaubelt; Tobias Schraink; Zhiao Shi; Richard D. Smith; Xiaoyu Song; Jimin Tan; Ratna R. Thangudu; Nicole Tignor; Joshua M. Wang; Pei Wang; Ying (Cindy) Wang; Bo Wen; Maciej Wiznerowicz; Xinpei Yi; Bing Zhang; Hui Zhang; Xu Zhang; Zhen Zhang

doi:10.1016/j.cell.2023.07.014

Pan-cancer proteogenomics connects oncogenic drivers to functional states

Clinical Proteomic Tumor Analysis Consortium, Yize Li, Eduard Porta-Pardo, Collin Tokheim, Matthew H. Bailey, Tomer M. Yaron, Vasileios Stathias, Yifat Geffen, Kathleen J. Imbach, Song Cao, Shankara Anand, Yo Akiyama, Wenke Liu, Matthew A. Wyczalkowski, Yizhe Song, Erik P. Storrs, Michael C. Wendl, Wubing Zhang, Mustafa Sibai, Victoria Ruiz-SerraWen Wei Liang, Nadezhda V. Terekhanova, Fernanda Martins Rodrigues, Karl R. Clauser, David I. Heiman, Qing Zhang, Francois Aguet, Anna P. Calinawan, Saravana M. Dhanasekaran, Chet Birger, Shankha Satpathy, Daniel Cui Zhou, Liang Bo Wang, Jessika Baral, Jared L. Johnson, Emily M. Huntsman, Pietro Pugliese, Antonio Colaprico, Antonio Iavarone, Milan G. Chheda, Christopher J. Ricketts, David Fenyö, Samuel H. Payne, Henry Rodriguez, Ana I. Robles, Michael A. Gillette, Chandan Kumar-Sinha, Alexander J. Lazar, Lewis C. Cantley, Gad Getz, Li Ding, Eunkyung An, Meenakshi Anurag, Jasmin Bavarva, Michael J. Birrer, Anna Calinawan, Michele Ceccarelli, Daniel W. Chan, Arul M. Chinnaiyan, Hanbyul Cho, Shrabanti Chowdhury, Marcin P. Cieslik, Felipe da Veiga Leprevost, Corbin Day, Marcin J. Domagalski, Yongchao Dou, Brian J. Druker, Nathan Edwards, Matthew J. Ellis, Myvizhi Esai Selvan, Steven M. Foltz, Alicia Francis, Tania J. Gonzalez Robles, Sara J.C. Gosline, Zeynep H. Gümüş, Tara Hiltke, Runyu Hong, Galen Hostetter, Yingwei Hu, Chen Huang, Emily Huntsman, Eric J. Jaehnig, Scott D. Jewel, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A. Ketchum, Iga Kolodziejczak, Jonathan T. Lei, Yuxing Liao, Caleb M. Lindgren, Tao Liu, Weiping Ma, Wilson McKerrow, Alexey I. Nesvizhskii, Chelsea Newton, Robert Oldroyd, Gilbert S. Omenn, Amanda G. Paulovich, Francesca Petralia, Boris Reva, Karin D. Rodland, Kelly V. Ruggles, Dmitry Rykunov, Sara R. Savage, Eric E. Schadt, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Richard D. Smith, Xiaoyu Song, Jimin Tan, Ratna R. Thangudu, Nicole Tignor, Joshua M. Wang, Pei Wang, Ying (Cindy) Wang, Bo Wen, Maciej Wiznerowicz, Xinpei Yi, Bing Zhang, Hui Zhang, Xu Zhang, Zhen Zhang

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.

Original language	English
Pages (from-to)	3921-3944.e25
Journal	Cell
Volume	186
Issue number	18
DOIs	https://doi.org/10.1016/j.cell.2023.07.014
State	Published - Aug 31 2023

Keywords

CPTAC
cancer hallmark
oncogenic driver
pan-cancer
phosphoproteomics
protein complex
proteogenomics
proteomics
therapeutic target

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10.1016/j.cell.2023.07.014

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Clinical Proteomic Tumor Analysis Consortium, Li, Y., Porta-Pardo, E., Tokheim, C., Bailey, M. H., Yaron, T. M., Stathias, V., Geffen, Y., Imbach, K. J., Cao, S., Anand, S., Akiyama, Y., Liu, W., Wyczalkowski, M. A., Song, Y., Storrs, E. P., Wendl, M. C., Zhang, W., Sibai, M., ... Zhang, Z. (2023). Pan-cancer proteogenomics connects oncogenic drivers to functional states. Cell, 186(18), 3921-3944.e25. https://doi.org/10.1016/j.cell.2023.07.014

@article{6b5a8782b91e42aa93223ea326997ee3,

title = "Pan-cancer proteogenomics connects oncogenic drivers to functional states",

abstract = "Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.",

keywords = "CPTAC, cancer hallmark, oncogenic driver, pan-cancer, phosphoproteomics, protein complex, proteogenomics, proteomics, therapeutic target",

author = "{Clinical Proteomic Tumor Analysis Consortium} and Yize Li and Eduard Porta-Pardo and Collin Tokheim and Bailey, {Matthew H.} and Yaron, {Tomer M.} and Vasileios Stathias and Yifat Geffen and Imbach, {Kathleen J.} and Song Cao and Shankara Anand and Yo Akiyama and Wenke Liu and Wyczalkowski, {Matthew A.} and Yizhe Song and Storrs, {Erik P.} and Wendl, {Michael C.} and Wubing Zhang and Mustafa Sibai and Victoria Ruiz-Serra and Liang, {Wen Wei} and Terekhanova, {Nadezhda V.} and Rodrigues, {Fernanda Martins} and Clauser, {Karl R.} and Heiman, {David I.} and Qing Zhang and Francois Aguet and Calinawan, {Anna P.} and Dhanasekaran, {Saravana M.} and Chet Birger and Shankha Satpathy and Zhou, {Daniel Cui} and Wang, {Liang Bo} and Jessika Baral and Johnson, {Jared L.} and Huntsman, {Emily M.} and Pietro Pugliese and Antonio Colaprico and Antonio Iavarone and Chheda, {Milan G.} and Ricketts, {Christopher J.} and David Feny{\"o} and Payne, {Samuel H.} and Henry Rodriguez and Robles, {Ana I.} and Gillette, {Michael A.} and Chandan Kumar-Sinha and Lazar, {Alexander J.} and Cantley, {Lewis C.} and Gad Getz and Li Ding and Eunkyung An and Meenakshi Anurag and Jasmin Bavarva and Birrer, {Michael J.} and Anna Calinawan and Michele Ceccarelli and Chan, {Daniel W.} and Chinnaiyan, {Arul M.} and Hanbyul Cho and Shrabanti Chowdhury and Cieslik, {Marcin P.} and {da Veiga Leprevost}, Felipe and Corbin Day and Domagalski, {Marcin J.} and Yongchao Dou and Druker, {Brian J.} and Nathan Edwards and Ellis, {Matthew J.} and Selvan, {Myvizhi Esai} and Foltz, {Steven M.} and Alicia Francis and {Gonzalez Robles}, {Tania J.} and Gosline, {Sara J.C.} and G{\"u}m{\"u}{\c s}, {Zeynep H.} and Tara Hiltke and Runyu Hong and Galen Hostetter and Yingwei Hu and Chen Huang and Emily Huntsman and Jaehnig, {Eric J.} and Jewel, {Scott D.} and Jiayi Ji and Wen Jiang and Lizabeth Katsnelson and Ketchum, {Karen A.} and Iga Kolodziejczak and Lei, {Jonathan T.} and Yuxing Liao and Lindgren, {Caleb M.} and Tao Liu and Weiping Ma and Wilson McKerrow and Nesvizhskii, {Alexey I.} and Chelsea Newton and Robert Oldroyd and Omenn, {Gilbert S.} and Paulovich, {Amanda G.} and Francesca Petralia and Boris Reva and Rodland, {Karin D.} and Ruggles, {Kelly V.} and Dmitry Rykunov and Savage, {Sara R.} and Schadt, {Eric E.} and Michael Schnaubelt and Tobias Schraink and Zhiao Shi and Smith, {Richard D.} and Xiaoyu Song and Jimin Tan and Thangudu, {Ratna R.} and Nicole Tignor and Wang, {Joshua M.} and Pei Wang and Wang, {Ying (Cindy)} and Bo Wen and Maciej Wiznerowicz and Xinpei Yi and Bing Zhang and Hui Zhang and Xu Zhang and Zhen Zhang",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

day = "31",

doi = "10.1016/j.cell.2023.07.014",

language = "English",

volume = "186",

pages = "3921--3944.e25",

journal = "Cell",

issn = "0092-8674",

number = "18",

}

Clinical Proteomic Tumor Analysis Consortium, Li, Y, Porta-Pardo, E, Tokheim, C, Bailey, MH, Yaron, TM, Stathias, V, Geffen, Y, Imbach, KJ, Cao, S, Anand, S, Akiyama, Y, Liu, W, Wyczalkowski, MA, Song, Y, Storrs, EP, Wendl, MC, Zhang, W, Sibai, M, Ruiz-Serra, V, Liang, WW, Terekhanova, NV, Rodrigues, FM, Clauser, KR, Heiman, DI, Zhang, Q, Aguet, F, Calinawan, AP, Dhanasekaran, SM, Birger, C, Satpathy, S, Zhou, DC, Wang, LB, Baral, J, Johnson, JL, Huntsman, EM, Pugliese, P, Colaprico, A, Iavarone, A, Chheda, MG, Ricketts, CJ, Fenyö, D, Payne, SH, Rodriguez, H, Robles, AI, Gillette, MA, Kumar-Sinha, C, Lazar, AJ, Cantley, LC, Getz, G, Ding, L, An, E, Anurag, M, Bavarva, J, Birrer, MJ, Calinawan, A, Ceccarelli, M, Chan, DW, Chinnaiyan, AM, Cho, H, Chowdhury, S, Cieslik, MP, da Veiga Leprevost, F, Day, C, Domagalski, MJ, Dou, Y, Druker, BJ, Edwards, N, Ellis, MJ, Selvan, ME, Foltz, SM, Francis, A, Gonzalez Robles, TJ, Gosline, SJC, Gümüş, ZH, Hiltke, T, Hong, R, Hostetter, G, Hu, Y, Huang, C, Huntsman, E, Jaehnig, EJ, Jewel, SD, Ji, J, Jiang, W, Katsnelson, L, Ketchum, KA, Kolodziejczak, I, Lei, JT, Liao, Y, Lindgren, CM, Liu, T, Ma, W, McKerrow, W, Nesvizhskii, AI, Newton, C, Oldroyd, R, Omenn, GS, Paulovich, AG, Petralia, F, Reva, B, Rodland, KD, Ruggles, KV, Rykunov, D, Savage, SR, Schadt, EE, Schnaubelt, M, Schraink, T, Shi, Z, Smith, RD, Song, X, Tan, J, Thangudu, RR, Tignor, N, Wang, JM, Wang, P, Wang, Y, Wen, B, Wiznerowicz, M, Yi, X, Zhang, B, Zhang, H, Zhang, X & Zhang, Z 2023, 'Pan-cancer proteogenomics connects oncogenic drivers to functional states', Cell, vol. 186, no. 18, pp. 3921-3944.e25. https://doi.org/10.1016/j.cell.2023.07.014

TY - JOUR

T1 - Pan-cancer proteogenomics connects oncogenic drivers to functional states

AU - Clinical Proteomic Tumor Analysis Consortium

AU - Li, Yize

AU - Porta-Pardo, Eduard

AU - Tokheim, Collin

AU - Bailey, Matthew H.

AU - Yaron, Tomer M.

AU - Stathias, Vasileios

AU - Geffen, Yifat

AU - Imbach, Kathleen J.

AU - Cao, Song

AU - Anand, Shankara

AU - Akiyama, Yo

AU - Liu, Wenke

AU - Wyczalkowski, Matthew A.

AU - Song, Yizhe

AU - Storrs, Erik P.

AU - Wendl, Michael C.

AU - Zhang, Wubing

AU - Sibai, Mustafa

AU - Ruiz-Serra, Victoria

AU - Liang, Wen Wei

AU - Terekhanova, Nadezhda V.

AU - Rodrigues, Fernanda Martins

AU - Clauser, Karl R.

AU - Heiman, David I.

AU - Zhang, Qing

AU - Aguet, Francois

AU - Calinawan, Anna P.

AU - Dhanasekaran, Saravana M.

AU - Birger, Chet

AU - Satpathy, Shankha

AU - Zhou, Daniel Cui

AU - Wang, Liang Bo

AU - Baral, Jessika

AU - Johnson, Jared L.

AU - Huntsman, Emily M.

AU - Pugliese, Pietro

AU - Colaprico, Antonio

AU - Iavarone, Antonio

AU - Chheda, Milan G.

AU - Ricketts, Christopher J.

AU - Fenyö, David

AU - Payne, Samuel H.

AU - Rodriguez, Henry

AU - Robles, Ana I.

AU - Gillette, Michael A.

AU - Kumar-Sinha, Chandan

AU - Lazar, Alexander J.

AU - Cantley, Lewis C.

AU - Getz, Gad

AU - Ding, Li

AU - An, Eunkyung

AU - Anurag, Meenakshi

AU - Bavarva, Jasmin

AU - Birrer, Michael J.

AU - Calinawan, Anna

AU - Ceccarelli, Michele

AU - Chan, Daniel W.

AU - Chinnaiyan, Arul M.

AU - Cho, Hanbyul

AU - Chowdhury, Shrabanti

AU - Cieslik, Marcin P.

AU - da Veiga Leprevost, Felipe

AU - Day, Corbin

AU - Domagalski, Marcin J.

AU - Dou, Yongchao

AU - Druker, Brian J.

AU - Edwards, Nathan

AU - Ellis, Matthew J.

AU - Selvan, Myvizhi Esai

AU - Foltz, Steven M.

AU - Francis, Alicia

AU - Gonzalez Robles, Tania J.

AU - Gosline, Sara J.C.

AU - Gümüş, Zeynep H.

AU - Hiltke, Tara

AU - Hong, Runyu

AU - Hostetter, Galen

AU - Hu, Yingwei

AU - Huang, Chen

AU - Huntsman, Emily

AU - Jaehnig, Eric J.

AU - Jewel, Scott D.

AU - Ji, Jiayi

AU - Jiang, Wen

AU - Katsnelson, Lizabeth

AU - Ketchum, Karen A.

AU - Kolodziejczak, Iga

AU - Lei, Jonathan T.

AU - Liao, Yuxing

AU - Lindgren, Caleb M.

AU - Liu, Tao

AU - Ma, Weiping

AU - McKerrow, Wilson

AU - Nesvizhskii, Alexey I.

AU - Newton, Chelsea

AU - Oldroyd, Robert

AU - Omenn, Gilbert S.

AU - Paulovich, Amanda G.

AU - Petralia, Francesca

AU - Reva, Boris

AU - Rodland, Karin D.

AU - Ruggles, Kelly V.

AU - Rykunov, Dmitry

AU - Savage, Sara R.

AU - Schadt, Eric E.

AU - Schnaubelt, Michael

AU - Schraink, Tobias

AU - Shi, Zhiao

AU - Smith, Richard D.

AU - Song, Xiaoyu

AU - Tan, Jimin

AU - Thangudu, Ratna R.

AU - Tignor, Nicole

AU - Wang, Joshua M.

AU - Wang, Pei

AU - Wang, Ying (Cindy)

AU - Wen, Bo

AU - Wiznerowicz, Maciej

AU - Yi, Xinpei

AU - Zhang, Bing

AU - Zhang, Hui

AU - Zhang, Xu

AU - Zhang, Zhen

PY - 2023/8/31

Y1 - 2023/8/31

N2 - Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.

AB - Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.

KW - CPTAC

KW - cancer hallmark

KW - oncogenic driver

KW - pan-cancer

KW - phosphoproteomics

KW - protein complex

KW - proteogenomics

KW - proteomics

KW - therapeutic target

UR - http://www.scopus.com/inward/record.url?scp=85169624163&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.07.014

DO - 10.1016/j.cell.2023.07.014

M3 - Article

C2 - 37582357

AN - SCOPUS:85169624163

SN - 0092-8674

VL - 186

SP - 3921-3944.e25

JO - Cell

JF - Cell

IS - 18

ER -

Pan-cancer proteogenomics connects oncogenic drivers to functional states

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Keywords

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