New and Novel Treatments for Gynecologic CancerCharacterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational ModelingBI, JIANLING PhD*; THIEL, KRISTINA W. PhD*; LITMAN, JACOB M. PhD†; ZHANG, YUPING MS*; DEVOR, ERIC J. PhD*,‡; NEWTSON, ANDREEA M. MD*; SCHNIEDERS, MICHAEL J. PhD§,∥; GONZALEZ BOSQUET, JESUS MD, PhD*; LESLIE, KIMBERLY K. MD*,‡Author Information Departments of *Obstetrics and Gynecology ∥Biochemistry §Biomedical Engineering ‡Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa †Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, Texas J.B. and K.W.T. contributed equally. Supported in part by the National Institutes of Health (R01CA099908 to K.K.L. and R01CA184101 to K.K.L.), National Science Foundation (CHE-1751688 to M.J.S.) and the University of Texas at Austin (Donald D. Harrington Faculty Fellowship to M.J.S.). The funders had no role in study design, data interpretation or decision to publish. K.W.T.: is a cofounder of Immortagen Inc., and holds an equity stake in the Company. The remaining authors declare that they have nothing to disclose. Correspondence: Kimberly K. Leslie, MD, Jennifer Niebyl Chair, and DEO, Department of Obstetrics and Gynecology, University of Iowa, 31140 PFP, 200 Hawkins Drive, Iowa City, IA. E-mail: email@example.com Clinical Obstetrics and Gynecology: March 2020 - Volume 63 - Issue 1 - p 109-119 doi: 10.1097/GRF.0000000000000516 Buy Metrics Abstract In our proof-of-concept study of 1 patient with stage IIIC carcinosarcoma of the ovary, we discovered a rare mutation in the tumor suppressor, TP53, that results in the deletion of N131. Immunofluorescence imaging of the organoid culture revealed hyperstaining of p53 protein. Computational modeling suggests this residue is important for maintaining protein conformation. Drug screening identified the combination of a proteasome inhibitor with a histone deacetylase inhibitor as the most effective treatment. These data provide evidence for the successful culture of a patient tumor and analysis of drug response ex vivo. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.