Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma | Zendy

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Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Author(s) -

Michael A. Gillette,

Shankha Satpathy,

Song Cao,

Saravana M. Dhanasekaran,

Suhas Vasaikar,

Karsten Krug,

Francesca Petralia,

Yize Li,

Wen-Wei Liang,

Boris Reva,

Azra Krek,

Jiayi Ji,

Xiaoyu Song,

Wenke Liu,

Runyu Hong,

Lijun Yao,

Lili M. Blumenberg,

Sara R. Savage,

Michael C. Wendl,

Bo Wen,

Kai Li,

Lauren C. Tang,

Melanie A. MacMullan,

Shayan C. Avanessian,

M. Harry Kane,

Chelsea J. Newton,

MacIntosh Cornwell,

Ramani Kothadia,

Weiping Ma,

Seungyeul Yoo,

Rahul Mannan,

Pankaj Vats,

Chandan KumarSinha,

Emily Kawaler,

Tatiana Omelchenko,

Antonio Colaprico,

Yifat Geffen,

Yosef E. Maruvka,

Felipe da Veiga Leprevost,

Maciej Wiznerowicz,

Zeynep H. Gümüş,

Rajwanth Veluswamy,

Galen Hostetter,

David I. Heiman,

Matthew A. Wyczalkowski,

Tara Hiltke,

Mehdi Mesri,

Christopher R. Kinsinger,

Emily S. Boja,

Gilbert S. Omenn,

Arul M. Chinnaiyan,

Henry Rodriguez,

Qing Kay Li,

Scott D. Jewell,

Mathangi Thiagarajan,

Gad Getz,

Bing Zhang,

David Fenyö,

Kelly V. Ruggles,

Marcin Cieślik,

Ana I. Robles,

Karl R. Clauser,

Ramaswamy Govindan,

Pei Wang,

Alexey I. Nesvizhskii,

Li Ding,

D.R. Mani,

Steven A. Carr,

Alex Webster,

Alicia Francis,

Alyssa Charamut,

Amanda G. Paulovich,

Amy M. Perou,

Andrew K. Godwin,

Andrii Karnuta,

Annette Marrero-Oliveras,

Barbara Hindenach,

Barbara L. Pruetz,

Bartosz Kubisa,

Brian J. Druker,

Chet Birger,

Corbin D. Jones,

Dana R. Valley,

Daniel C. Rohrer,

Daniel Cui Zhou,

Daniel W. Chan,

David Chesla,

David Clark,

Dmitry Rykunov,

Donghui Tan,

Elena V. Ponomareva,

Elizabeth R. Duffy,

Eric Burks,

Eric E. Schadt,

Erik J. Bergstrom,

Eugene S. Fedorov,

Ewa P. Malc,

George D. Wilson,

Haiquan Chen,

Halina Krzystek,

Hongwei Liu,

Houston Culpepper,

Hua Sun,

Hui Zhang,

Jacob Day,

James Suh,

Jeffrey R. Whiteaker,

Jennifer Eschbacher,

John P. McGee,

Karen A. Ketchum,

Karin Rodland,

Karna Robinson,

Katherine A. Hoadley,

Kei Suzuki,

Ki Sung Um,

Kim Elburn,

Liang-Bo Wang,

Lijun Chen,

Linda I. Hannick,

Liqun Qi,

Lori J. Sokoll,

Małgorzata Wojtyś,

Marcin J. Domagalski,

Marina Gritsenko,

Mary Beth Beasley,

Matthew Monroe,

Matthew J. Ellis,

Maureen A. Dyer,

Meghan C. Burke,

Melissa Borucki,

Menghong Sun,

Michael H. A. Roehrl,

Michael J. Birrer,

Michael S. Noble,

Michael Schnaubelt,

Michael W. Ver,

Michelle Chaikin,

Mikhail Krotevich,

Munziba Khan,

Myvizhi Esai Selvan,

Nancy Roche,

Nathan Edwards,

Negin Vatanian,

Olga Potapova,

Pamela Grady,

Peter B. McGarvey,

Piotr A. Mieczkowski,

Pushpa Hariharan,

Rashna Madan,

Ratna R. Thangudu,

Richard Smith,

Robert Welsh,

Robert Zelt,

Rohit Mehra,

Ronald Matteotti,

Sailaja Mareedu,

Samuel Payne,

Sandra Cottingham,

Sanford P. Markey,

Seema Chugh,

Shaleigh Smith,

Shirley Tsang,

Shuang Cai,

Simina M. Boca,

Sonya Carter,

Stacey Gabriel,

Stephanie Young,

Stephen E. Stein,

Sunita Shankar,

Tanya Krubit,

Tao Liu,

Tara Skelly,

Thomas Bauer,

Uma Velvulou,

Umut Özbek,

Vladislav Petyuk,

Volodymyr Sovenko,

William Bocik,

William W. Maggio,

Xi Chen,

Yan Shi,

Yige Wu,

Yingwei Hu,

Yuxing Liao,

Zhen Zhang,

Zhiao Shi

Publication year - 2020

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.2020.06.013

Subject(s) - proteogenomics , biology , proteomics , computational biology , phosphoproteomics , adenocarcinoma , epigenomics , genomics , bioinformatics , cancer research , genetics , cancer , gene , genome , dna methylation , protein kinase a , phosphorylation , gene expression , protein phosphorylation

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.

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