A proteogenomic portrait of lung squamous cell carcinoma

Shankha Satpathy; Karsten Krug; Pierre M Jean Beltran; Sara R Savage; Francesca Petralia; Chandan Kumar-Sinha; Yongchao Dou; Boris Reva; M Harry Kane; Shayan C Avanessian; Suhas V Vasaikar; Azra Krek; Jonathan T Lei; Eric J Jaehnig; Tatiana Omelchenko; Yifat Geffen; Erik J Bergstrom; Vasileios Stathias; Karen E Christianson; David I Heiman; Marcin P Cieslik; Song Cao; Xiaoyu Song; Jiayi Ji; Wenke Liu; Kai Li; Bo Wen; Yize Li; Zeynep H Gümüş; Myvizhi Esai Selvan; Rama Soundararajan; Tanvi H Visal; Maria G Raso; Edwin Roger Parra; Özgün Babur; Pankaj Vats; Shankara Anand; Tobias Schraink; MacIntosh Cornwell; Fernanda Martins Rodrigues; Houxiang Zhu; Chia-Kuei Mo; Yuping Zhang; Felipe da Veiga Leprevost; Chen Huang; Arul M Chinnaiyan; Matthew A Wyczalkowski; Gilbert S Omenn; Chelsea J Newton; Stephan Schurer; Kelly V Ruggles; David Fenyö; Scott D Jewell; Mathangi Thiagarajan; Mehdi Mesri; Henry Rodriguez; Sendurai A Mani; Namrata D Udeshi; Gad Getz; James Suh; Qing Kay Li; Galen Hostetter; Paul K Paik; Saravana M Dhanasekaran; Ramaswamy Govindan; Li Ding; Ana I Robles; Karl R Clauser; Alexey I Nesvizhskii; Pei Wang; Steven A Carr; Bing Zhang; D R Mani; Michael A Gillette; Clinical Proteomic Tumor Analysis Consortium

doi:10.1016/j.cell.2021.07.016

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A proteogenomic portrait of lung squamous cell carcinoma

Journal article

Open access

Peer reviewed

A proteogenomic portrait of lung squamous cell carcinoma

Shankha Satpathy, Karsten Krug, Pierre M Jean Beltran, Sara R Savage, Francesca Petralia, Chandan Kumar-Sinha, Yongchao Dou, Boris Reva, M Harry Kane, Shayan C Avanessian, …

Cell, Vol.184(16), pp.4348-4371.e40

2021-08-05

DOI: https://doi.org/10.1016/j.cell.2021.07.016

PMID: 34358469

Abstract

Acetylation

Adult

Aged

Aged, 80 and over

Carcinoma, Squamous Cell - genetics

Cluster Analysis

Cyclin-Dependent Kinase 4 - genetics

Cyclin-Dependent Kinase 6 - genetics

Epithelial-Mesenchymal Transition - genetics

Female

Gene Expression Regulation, Neoplastic

Humans

Lung Neoplasms - genetics

Male

Middle Aged

Mutation - genetics

Neoplasm Proteins - metabolism

Phosphorylation

Protein Binding

Proteogenomics

Receptor Tyrosine Kinase-like Orphan Receptors - metabolism

Receptors, Platelet-Derived Growth Factor - metabolism

Signal Transduction

Ubiquitination

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

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Collaboration types: Domestic collaboration
Citation topics: 2 Chemistry; 2.211 Mass Spectrometry; 2.211.497 Proteomics
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: A proteogenomic portrait of lung squamous cell carcinoma
Creators: Shankha Satpathy - Massachusetts Institute of Technology
Karsten Krug - Massachusetts Institute of Technology
Pierre M Jean Beltran - Massachusetts Institute of Technology
Sara R Savage - Baylor College of Medicine
Francesca Petralia - Icahn School of Medicine at Mount Sinai
Chandan Kumar-Sinha - University of Michigan–Ann Arbor
Yongchao Dou - Baylor College of Medicine
Boris Reva - Icahn School of Medicine at Mount Sinai
M Harry Kane - Massachusetts Institute of Technology
Shayan C Avanessian - Massachusetts Institute of Technology
Suhas V Vasaikar - The University of Texas MD Anderson Cancer Center
Azra Krek - Icahn School of Medicine at Mount Sinai
Jonathan T Lei - Baylor College of Medicine
Eric J Jaehnig - Baylor College of Medicine
Tatiana Omelchenko - Memorial Sloan Kettering Cancer Center
Yifat Geffen - Massachusetts Institute of Technology
Erik J Bergstrom - Massachusetts Institute of Technology
Vasileios Stathias - Sylvester Comprehensive Cancer Center
Karen E Christianson - Massachusetts Institute of Technology
David I Heiman - Massachusetts Institute of Technology
Marcin P Cieslik - University of Michigan–Ann Arbor
Song Cao - Washington University in St. Louis
Xiaoyu Song - Icahn School of Medicine at Mount Sinai
Jiayi Ji - Icahn School of Medicine at Mount Sinai
Wenke Liu - Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA
Kai Li - Baylor College of Medicine
Bo Wen - Baylor College of Medicine
Yize Li - Washington University in St. Louis
Zeynep H Gümüş - Icahn School of Medicine at Mount Sinai
Myvizhi Esai Selvan - Icahn School of Medicine at Mount Sinai
Rama Soundararajan - The University of Texas MD Anderson Cancer Center
Tanvi H Visal - The University of Texas MD Anderson Cancer Center
Maria G Raso - The University of Texas MD Anderson Cancer Center
Edwin Roger Parra - The University of Texas MD Anderson Cancer Center
Özgün Babur - University of Massachusetts Boston
Pankaj Vats - University of Michigan–Ann Arbor
Shankara Anand - Massachusetts Institute of Technology
Tobias Schraink - Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA
MacIntosh Cornwell - Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA
Fernanda Martins Rodrigues - Washington University in St. Louis
Houxiang Zhu - Washington University in St. Louis
Chia-Kuei Mo - Washington University in St. Louis
Yuping Zhang - University of Michigan–Ann Arbor
Felipe da Veiga Leprevost - University of Michigan–Ann Arbor
Chen Huang - Baylor College of Medicine
Arul M Chinnaiyan - University of Michigan–Ann Arbor
Matthew A Wyczalkowski - Washington University in St. Louis
Gilbert S Omenn - University of Michigan–Ann Arbor
Chelsea J Newton - Van Andel Research Institute, Grand Rapids, MI 49503, USA
Stephan Schurer - Sylvester Comprehensive Cancer Center
Kelly V Ruggles - Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA
David Fenyö - Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA
Scott D Jewell - Van Andel Research Institute, Grand Rapids, MI 49503, USA
Mathangi Thiagarajan - Frederick National Laboratory for Cancer Research
Mehdi Mesri - Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA
Henry Rodriguez - Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA
Sendurai A Mani - The University of Texas MD Anderson Cancer Center
Namrata D Udeshi - Massachusetts Institute of Technology
Gad Getz - Massachusetts Institute of Technology
James Suh - Frederick National Laboratory for Cancer Research
Qing Kay Li - Sidney Kimmel Comprehensive Cancer Center
Galen Hostetter - Van Andel Research Institute, Grand Rapids, MI 49503, USA
Paul K Paik - Memorial Sloan Kettering Cancer Center
Saravana M Dhanasekaran - University of Michigan–Ann Arbor
Ramaswamy Govindan - Washington University in St. Louis
Li Ding - Washington University in St. Louis
Ana I Robles - Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA
Karl R Clauser - Massachusetts Institute of Technology
Alexey I Nesvizhskii - University of Michigan–Ann Arbor
Pei Wang - Icahn School of Medicine at Mount Sinai
Steven A Carr - Massachusetts Institute of Technology
Bing Zhang - Baylor College of Medicine
D R Mani - Massachusetts Institute of Technology
Michael A Gillette - Massachusetts Institute of Technology
Clinical Proteomic Tumor Analysis Consortium
Publication Details: Cell, Vol.184(16), pp.4348-4371.e40
Grant note: U01 CA214125 / NCI NIH HHS U01 CA214116 / NCI NIH HHS F32 HL154711 / NHLBI NIH HHS U24 CA210955 / NCI NIH HHS U54 HL127624 / NHLBI NIH HHS U24 CA210972 / NCI NIH HHS U24 CA210985 / NCI NIH HHS U24 CA210954 / NCI NIH HHS U24 CA210979 / NCI NIH HHS U24 CA210993 / NCI NIH HHS U24 CA210967 / NCI NIH HHS U01 CA214114 / NCI NIH HHS P30 CA240139 / NCI NIH HHS U24 CA210986 / NCI NIH HHS T32 CA203690 / NCI NIH HHS
Academic Unit: Miller School of Medicine; Molecular and Cellular Pharmacology Research
Language: English
Resource Type: Journal article
PMID: 34358469
Record Identifier: 991031660527102976