Proteogenomic Characterization of Endometrial Carcinoma.

Cell (2020-02-16)
Yongchao Dou, Emily A Kawaler, Daniel Cui Zhou, Marina A Gritsenko, Chen Huang, Lili Blumenberg, Alla Karpova, Vladislav A Petyuk, Sara R Savage, Shankha Satpathy, Wenke Liu, Yige Wu, Chia-Feng Tsai, Bo Wen, Zhi Li, Song Cao, Jamie Moon, Zhiao Shi, MacIntosh Cornwell, Matthew A Wyczalkowski, Rosalie K Chu, Suhas Vasaikar, Hua Zhou, Qingsong Gao, Ronald J Moore, Kai Li, Sunantha Sethuraman, Matthew E Monroe, Rui Zhao, David Heiman, Karsten Krug, Karl Clauser, Ramani Kothadia, Yosef Maruvka, Alexander R Pico, Amanda E Oliphant, Emily L Hoskins, Samuel L Pugh, Sean J I Beecroft, David W Adams, Jonathan C Jarman, Andy Kong, Hui-Yin Chang, Boris Reva, Yuxing Liao, Dmitry Rykunov, Antonio Colaprico, Xi Steven Chen, Andrzej Czekański, Marcin Jędryka, Rafał Matkowski, Maciej Wiznerowicz, Tara Hiltke, Emily Boja, Christopher R Kinsinger, Mehdi Mesri, Ana I Robles, Henry Rodriguez, David Mutch, Katherine Fuh, Matthew J Ellis, Deborah DeLair, Mathangi Thiagarajan, D R Mani, Gad Getz, Michael Noble, Alexey I Nesvizhskii, Pei Wang, Matthew L Anderson, Douglas A Levine, Richard D Smith, Samuel H Payne, Kelly V Ruggles, Karin D Rodland, Li Ding, Bing Zhang, Tao Liu, David Fenyö
ABSTRACT

We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Sigma-Aldrich
Calcium chloride, anhydrous, granular, ≤7.0 mm, ≥93.0%
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Ethylenediaminetetraacetic acid disodium salt solution, for molecular biology, 0.5 M in H2O, DNase, RNase, NICKase and protease, none detected
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Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
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Phenylmethanesulfonyl fluoride solution, ~0.1 M in ethanol (T)
Sigma-Aldrich
PUGNAc, ≥95% (HPLC)
Sigma-Aldrich
Nα-Acetyl-L-lysine