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Cell. 2020 Feb 20;180(4):729-748.e26. doi: 10.1016/j.cell.2020.01.026. Epub 2020 Feb 13.

Proteogenomic Characterization of Endometrial Carcinoma.

Author information

1
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
2
Institute for Systems Genetics, NYU School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
3
Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
4
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
5
Department of Medicine, NYU School of Medicine, New York, NY 10016, USA.
6
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
7
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
8
Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA.
9
Department of Biology, Brigham Young University, Provo, UT 84602, USA.
10
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
11
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
12
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Division of Biostatistics, Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
13
Department of Oncology, Wroclaw Medical University, 50-367 Wrocław, Poland; Wroclaw Comprehensive Cancer Center, 53-413 Wrocław, Poland.
14
Poznan University of Medical Sciences, 61-701 Poznań, Poland; University Hospital of Lord's Transfiguration, 60-569 Poznań, Poland; International Institute for Molecular Oncology, 60-203 Poznań, Poland.
15
Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
16
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
17
Department of Pathology, NYU Langone Health, New York, NY 10016, USA.
18
Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
19
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
20
College of Medicine Obstetrics & Gynecology, University of South Florida Health, Tampa, FL 33620, USA.
21
Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, USA.
22
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA; Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97221, USA. Electronic address: karin.rodland@pnnl.gov.
23
Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA. Electronic address: lding@wustl.edu.
24
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: bing.zhang@bcm.edu.
25
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA. Electronic address: tao.liu@pnnl.gov.
26
Institute for Systems Genetics, NYU School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA. Electronic address: david@fenyolab.org.

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.

KEYWORDS:

CTNNB1; TP53; acetylation; circular RNA; endometrial cancer; endometrioid endometrial cancer; immune evasion; proteogenomics; proteomics; serous endometrial cancer

PMID:
32059776
DOI:
10.1016/j.cell.2020.01.026
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