Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Clinical Proteomic Tumor Analysis Consortium

doi:10.1016/j.cell.2020.06.013

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Clinical Proteomic Tumor Analysis Consortium

School of Medicine

Broad Institute
Massachusetts General Hospital
Washington University St. Louis
University of Michigan, Ann Arbor
University of Texas MD Anderson Cancer Center
Icahn School of Medicine at Mount Sinai
New York University
Baylor College of Medicine
Columbia University
University of Southern California
Van Andel Institute
Memorial Sloan-Kettering Cancer Center
University of Miami
University of Medical Sciences Poznan
International Institute for Molecular Oncology
National Institutes of Health

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

685 Scopus citations

Abstract

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

Original language	English
Pages (from-to)	200-225.e35
Journal	Cell
Volume	182
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2020.06.013
State	Published - 9 Jul 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CPTAC
acetylation
adenocarcinoma
genomics
lung cancer
mass spectrometry
phosphorylation
protein
proteogenomics
proteomics

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10.1016/j.cell.2020.06.013

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@article{d8b653f61fcb4d559cfdfdc94f815592,

title = "Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma",

abstract = "To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.",

keywords = "CPTAC, acetylation, adenocarcinoma, genomics, lung cancer, mass spectrometry, phosphorylation, protein, proteogenomics, proteomics",

author = "\{Clinical Proteomic Tumor Analysis Consortium\} and Gillette, \{Michael A.\} and Shankha Satpathy and Song Cao and Dhanasekaran, \{Saravana M.\} and Vasaikar, \{Suhas V.\} and Karsten Krug and Francesca Petralia and Yize Li and Liang, \{Wen Wei\} and Boris Reva and Azra Krek and Jiayi Ji and Xiaoyu Song and Wenke Liu and Runyu Hong and Lijun Yao and Lili Blumenberg and Savage, \{Sara R.\} and Wendl, \{Michael C.\} and Bo Wen and Kai Li and Tang, \{Lauren C.\} and MacMullan, \{Melanie A.\} and Avanessian, \{Shayan C.\} and Kane, \{M. Harry\} and Newton, \{Chelsea J.\} and MacIntosh Cornwell and Kothadia, \{Ramani B.\} and Weiping Ma and Seungyeul Yoo and Rahul Mannan and Pankaj Vats and Chandan Kumar-Sinha and Kawaler, \{Emily A.\} and Tatiana Omelchenko and Antonio Colaprico and Yifat Geffen and Maruvka, \{Yosef E.\} and \{da Veiga Leprevost\}, Felipe and Maciej Wiznerowicz and G{\"u}m{\"u}{\c s}, \{Zeynep H.\} and Veluswamy, \{Rajwanth R.\} and Galen Hostetter and Heiman, \{David I.\} and Wyczalkowski, \{Matthew A.\} and Tara Hiltke and Mehdi Mesri and Kinsinger, \{Christopher R.\} and Thomas Bauer and Maggio, \{William W.\}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = jul,

day = "9",

doi = "10.1016/j.cell.2020.06.013",

language = "English",

volume = "182",

pages = "200--225.e35",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "1",

}

TY - JOUR

T1 - Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

AU - Clinical Proteomic Tumor Analysis Consortium

AU - Gillette, Michael A.

AU - Satpathy, Shankha

AU - Cao, Song

AU - Dhanasekaran, Saravana M.

AU - Vasaikar, Suhas V.

AU - Krug, Karsten

AU - Petralia, Francesca

AU - Li, Yize

AU - Liang, Wen Wei

AU - Reva, Boris

AU - Krek, Azra

AU - Ji, Jiayi

AU - Song, Xiaoyu

AU - Liu, Wenke

AU - Hong, Runyu

AU - Yao, Lijun

AU - Blumenberg, Lili

AU - Savage, Sara R.

AU - Wendl, Michael C.

AU - Wen, Bo

AU - Li, Kai

AU - Tang, Lauren C.

AU - MacMullan, Melanie A.

AU - Avanessian, Shayan C.

AU - Kane, M. Harry

AU - Newton, Chelsea J.

AU - Cornwell, MacIntosh

AU - Kothadia, Ramani B.

AU - Ma, Weiping

AU - Yoo, Seungyeul

AU - Mannan, Rahul

AU - Vats, Pankaj

AU - Kumar-Sinha, Chandan

AU - Kawaler, Emily A.

AU - Omelchenko, Tatiana

AU - Colaprico, Antonio

AU - Geffen, Yifat

AU - Maruvka, Yosef E.

AU - da Veiga Leprevost, Felipe

AU - Wiznerowicz, Maciej

AU - Gümüş, Zeynep H.

AU - Veluswamy, Rajwanth R.

AU - Hostetter, Galen

AU - Heiman, David I.

AU - Wyczalkowski, Matthew A.

AU - Hiltke, Tara

AU - Mesri, Mehdi

AU - Kinsinger, Christopher R.

AU - Bauer, Thomas

AU - Maggio, William W.

PY - 2020/7/9

Y1 - 2020/7/9

N2 - To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

AB - To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

KW - CPTAC

KW - acetylation

KW - adenocarcinoma

KW - genomics

KW - lung cancer

KW - mass spectrometry

KW - phosphorylation

KW - protein

KW - proteogenomics

KW - proteomics

UR - https://www.scopus.com/pages/publications/85087400742

U2 - 10.1016/j.cell.2020.06.013

DO - 10.1016/j.cell.2020.06.013

M3 - Article

C2 - 32649874

AN - SCOPUS:85087400742

SN - 0092-8674

VL - 182

SP - 200-225.e35

JO - Cell

JF - Cell

IS - 1

ER -

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Abstract

UN SDGs

Keywords

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