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Proteogenomic insights suggest druggable pathways in endometrial carcinoma.
Dou, Yongchao; Katsnelson, Lizabeth; Gritsenko, Marina A; Hu, Yingwei; Reva, Boris; Hong, Runyu; Wang, Yi-Ting; Kolodziejczak, Iga; Lu, Rita Jui-Hsien; Tsai, Chia-Feng; Bu, Wen; Liu, Wenke; Guo, Xiaofang; An, Eunkyung; Arend, Rebecca C; Bavarva, Jasmin; Chen, Lijun; Chu, Rosalie K; Czekanski, Andrzej; Davoli, Teresa; Demicco, Elizabeth G; DeLair, Deborah; Devereaux, Kelly; Dhanasekaran, Saravana M; Dottino, Peter; Dover, Bailee; Fillmore, Thomas L; Foxall, McKenzie; Hermann, Catherine E; Hiltke, Tara; Hostetter, Galen; Jedryka, Marcin; Jewell, Scott D; Johnson, Isabelle; Kahn, Andrea G; Ku, Amy T; Kumar-Sinha, Chandan; Kurzawa, Pawel; Lazar, Alexander J; Lazcano, Rossana; Lei, Jonathan T; Li, Yi; Liao, Yuxing; Lih, Tung-Shing M; Lin, Tai-Tu; Martignetti, John A; Masand, Ramya P; Matkowski, Rafal; McKerrow, Wilson; Mesri, Mehdi.
Affiliation
  • Dou Y; 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.
  • Katsnelson L; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Gritsenko MA; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Hu Y; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Reva B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hong R; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Wang YT; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Kolodziejczak I; International Institute for Molecular Oncology, 20-203 Poznan, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.
  • Lu RJ; 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.
  • Tsai CF; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Bu W; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liu W; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Guo X; Division of Gynecologic Oncology, University of South Florida Morsani College of Medicine and Tampa General Hospital Cancer Institute, Tampa, FL 33606, USA.
  • An E; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
  • Arend RC; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL 35249, USA.
  • Bavarva J; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
  • Chen L; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Chu RK; Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Czekanski A; Wroclaw Medical University and Lower Silesian Oncology, Pulmonology and Hematology Center (DCOPIH), Wroclaw, Poland.
  • Davoli T; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Demicco EG; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1X5, Canada.
  • DeLair D; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Devereaux K; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Dhanasekaran SM; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Dottino P; Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Dover B; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL 35249, USA.
  • Fillmore TL; Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Foxall M; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL 35249, USA.
  • Hermann CE; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Hiltke T; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
  • Hostetter G; Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  • Jedryka M; Wroclaw Medical University and Lower Silesian Oncology, Pulmonology and Hematology Center (DCOPIH), Wroclaw, Poland.
  • Jewell SD; Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  • Johnson I; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Kahn AG; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35249, USA.
  • Ku AT; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Kumar-Sinha C; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kurzawa P; Heliodor Swiecicki Clinical Hospital in Poznan ul. Przybyszewskiego 49, 60-355 Poznan, Poland; Poznan University of Medical Sciences, 61-701 Poznan, Poland.
  • Lazar AJ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lazcano R; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lei JT; 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.
  • Li Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liao Y; 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.
  • Lih TM; Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Lin TT; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
  • Martignetti JA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Masand RP; Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Matkowski R; Wroclaw Medical University and Lower Silesian Oncology, Pulmonology and Hematology Center (DCOPIH), Wroclaw, Poland.
  • McKerrow W; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Mesri M; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
Cancer Cell ; 41(9): 1586-1605.e15, 2023 09 11.
Article in En | MEDLINE | ID: mdl-37567170
ABSTRACT
We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of ß-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endometrial Neoplasms / Proteogenomics / Metformin Type of study: Observational_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endometrial Neoplasms / Proteogenomics / Metformin Type of study: Observational_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2023 Document type: Article Affiliation country: