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Proteogenomic Characterization of Endometrial Carcinoma.


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/?-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.

SUBMITTER: Dou Y 

PROVIDER: S-EPMC7233456 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Proteogenomic Characterization of Endometrial Carcinoma.

Dou Yongchao Y   Kawaler Emily A EA   Cui Zhou Daniel D   Gritsenko Marina A MA   Huang Chen C   Blumenberg Lili L   Karpova Alla A   Petyuk Vladislav A VA   Savage Sara R SR   Satpathy Shankha S   Liu Wenke W   Wu Yige Y   Tsai Chia-Feng CF   Wen Bo B   Li Zhi Z   Cao Song S   Moon Jamie J   Shi Zhiao Z   Cornwell MacIntosh M   Wyczalkowski Matthew A MA   Chu Rosalie K RK   Vasaikar Suhas S   Zhou Hua H   Gao Qingsong Q   Moore Ronald J RJ   Li Kai K   Sethuraman Sunantha S   Monroe Matthew E ME   Zhao Rui R   Heiman David D   Krug Karsten K   Clauser Karl K   Kothadia Ramani R   Maruvka Yosef Y   Pico Alexander R AR   Oliphant Amanda E AE   Hoskins Emily L EL   Pugh Samuel L SL   Beecroft Sean J I SJI   Adams David W DW   Jarman Jonathan C JC   Kong Andy A   Chang Hui-Yin HY   Reva Boris B   Liao Yuxing Y   Rykunov Dmitry D   Colaprico Antonio A   Chen Xi Steven XS   Czekański Andrzej A   Jędryka Marcin M   Matkowski Rafał R   Wiznerowicz Maciej M   Hiltke Tara T   Boja Emily E   Kinsinger Christopher R CR   Mesri Mehdi M   Robles Ana I AI   Rodriguez Henry H   Mutch David D   Fuh Katherine K   Ellis Matthew J MJ   DeLair Deborah D   Thiagarajan Mathangi M   Mani D R DR   Getz Gad G   Noble Michael M   Nesvizhskii Alexey I AI   Wang Pei P   Anderson Matthew L ML   Levine Douglas A DA   Smith Richard D RD   Payne Samuel H SH   Ruggles Kelly V KV   Rodland Karin D KD   Ding Li L   Zhang Bing B   Liu Tao T   Fenyö David D  

Cell 20200213 4


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  ...[more]

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