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 - Govindan, Ramaswamy
AU - Ding, Li
N1 - Funding Information:
This work was supported by the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) grants U24CA210986 , U01CA214125 , U24CA210979 , U24CA210954 , U24CA210972 , U24CA210967 , and U24CA210993 and National Institute of Environmental Health Sciences grant P30ES017885 .
Funding Information:
B.Z. has received research funding from Bristol-Myers Squibb. All other authors have no conflict of interests to declare.
Publisher Copyright:
© 2020 Elsevier Inc.
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 - http://www.scopus.com/inward/record.url?scp=85087400742&partnerID=8YFLogxK
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 -