Characterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling

• Published in: Clinical obstetrics and gynecology Vol. 63; no. 1; p. 109
• Main Authors: Bi, Jianling, Thiel, Kristina W, Litman, Jacob M, Zhang, Yuping, Devor, Eric J, Newtson, Andreea M, Schnieders, Michael J, Gonzalez Bosquet, Jesus, Leslie, Kimberly K
• Format: Journal Article
• Language: English
• Published: United States 01.03.2020
• Subjects: Carcinoma, Ovarian Epithelial - genetics; Female; Genetic Predisposition to Disease; Humans; Organoids - metabolism; Ovarian Neoplasms - genetics; Patient-Specific Modeling; Tumor Suppressor Protein p53 - genetics
• ISSN: 1532-5520
• DOI: 10.1097/GRF.0000000000000516

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.