@article{8c6126c4585840729258fd2846f76b28,
title = "A proteogenomic portrait of lung squamous cell carcinoma",
abstract = "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.",
keywords = "CPTAC, acetylation, genomics, lung cancer, phosphorylation, protein, proteogenomics, proteomics, squamous, ubiquitylation",
author = "{Clinical Proteomic Tumor Analysis Consortium} and Shankha Satpathy and Karsten Krug and {Jean Beltran}, {Pierre M.} and Savage, {Sara R.} and Francesca Petralia and Chandan Kumar-Sinha and Yongchao Dou and Boris Reva and Kane, {M. Harry} and Avanessian, {Shayan C.} and Vasaikar, {Suhas V.} and Azra Krek and Lei, {Jonathan T.} and Jaehnig, {Eric J.} and Tatiana Omelchenko and Yifat Geffen and Bergstrom, {Erik J.} and Vasileios Stathias and Christianson, {Karen E.} and Heiman, {David I.} and Cieslik, {Marcin P.} and Song Cao and Xiaoyu Song and Jiayi Ji and Wenke Liu and Kai Li and Bo Wen and Yize Li and G{\"u}m{\"u}{\c s}, {Zeynep H.} and Selvan, {Myvizhi Esai} and Rama Soundararajan and Visal, {Tanvi H.} and Raso, {Maria G.} and Parra, {Edwin Roger} and {\"O}zg{\"u}n Babur and Pankaj Vats and Shankara Anand and Tobias Schraink and MacIntosh Cornwell and Rodrigues, {Fernanda Martins} and Houxiang Zhu and Mo, {Chia Kuei} and Yuping Zhang and {da Veiga Leprevost}, Felipe and Chen Huang and Chinnaiyan, {Arul M.} and Wyczalkowski, {Matthew A.} and Druker, {Brian J.} and Donna Hansel and Wohaib Hasan",
note = "Funding Information: This work was supported by the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) grants U24CA210955 , U24CA210985 , U24CA210986 , U24CA210954 , U24CA210967 , U24CA210972 , U24CA210979 , U24CA210993 , U01CA214114 , U01CA214116 , and U01CA214125 and NIH grants U54HL127624 , P30CA240139 , 1F32HL154711-01 , and T32CA203690 . We thank Dr. Lata Adnani for helping with graphics. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = aug,
day = "5",
doi = "10.1016/j.cell.2021.07.016",
language = "English (US)",
volume = "184",
pages = "4348--4371.e40",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "16",
}