Proteogenomic Characterization of Endometrial Carcinoma.
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.
Dou Y, Kawaler EA, Cui Zhou D, Gritsenko MA, Huang C, Blumenberg L, Karpova A, Petyuk VA, Savage SR, Satpathy S, Liu W, Wu Y, Tsai CF, Wen B, Li Z, Cao S, Moon J, Shi Z, Cornwell M, Wyczalkowski MA, Chu RK, Vasaikar S, Zhou H, Gao Q, Moore RJ, Li K, Sethuraman S, Monroe ME, Zhao R, Heiman D, Krug K, Clauser K, Kothadia R, Maruvka Y, Pico AR, Oliphant AE, Hoskins EL, Pugh SL, Beecroft SJI, Adams DW, Jarman JC, Kong A, Chang HY, Reva B, Liao Y, Rykunov D, Colaprico A, Chen XS, Czekański A, Jędryka M, Matkowski R, Wiznerowicz M, Hiltke T, Boja E, Kinsinger CR, Mesri M, Robles AI, Rodriguez H, Mutch D, Fuh K, Ellis MJ, DeLair D, Thiagarajan M, Mani DR, Getz G, Noble M, Nesvizhskii AI, Wang P, Anderson ML, Levine DA, Smith RD, Payne SH, Ruggles KV, Rodland KD, Ding L, Zhang B, Liu T, Fenyö D; Clinical Proteomic Tumor Analysis Consortium. Proteogenomic Characterization of Endometrial Carcinoma. Cell. 2020 Feb 20;180(4):729-748.e26. doi: 10.1016/j.cell.2020.01.026. Epub 2020 Feb 13. PMID: 32059776; PMCID: PMC7233456.