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

Jianling Bi; Kristina W Thiel; Jacob M Litman; Yuping Zhang; Eric J Devor; Andreea M Newtson; Michael J Schnieders; Jesus Gonzalez Bosquet; Kimberly K Leslie

doi:10.1097/GRF.0000000000000516

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

Journal article

Peer reviewed

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

Jianling Bi, Kristina W Thiel, Jacob M Litman, Yuping Zhang, Eric J Devor, Andreea M Newtson, Michael J Schnieders, Jesus Gonzalez Bosquet and Kimberly K Leslie

Clinical obstetrics and gynecology, Vol.63(1), pp.109-119

03/2020

DOI: 10.1097/GRF.0000000000000516

PMCID: PMC7521672

PMID: 31876640

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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.

Carcinoma, Ovarian Epithelial - genetics

Female

Genetic Predisposition to Disease

Humans

Organoids - metabolism

Ovarian Neoplasms - genetics

Patient-Specific Modeling

Tumor Suppressor Protein p53 - genetics

Details

Title: Subtitle: Characterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling
Creators: Jianling Bi - Departments of Obstetrics and Gynecology.
Kristina W Thiel - Departments of Obstetrics and Gynecology.
Jacob M Litman - University of Texas at Austin
Yuping Zhang - Departments of Obstetrics and Gynecology.
Eric J Devor - University of Iowa
Andreea M Newtson - Departments of Obstetrics and Gynecology.
Michael J Schnieders - Biomedical Engineering
Jesus Gonzalez Bosquet - Departments of Obstetrics and Gynecology
Kimberly K Leslie - University of Iowa
Resource Type: Journal article
Publication Details: Clinical obstetrics and gynecology, Vol.63(1), pp.109-119
DOI: 10.1097/GRF.0000000000000516
PMID: 31876640
PMCID: PMC7521672
NLM abbreviation: Clin Obstet Gynecol
ISSN: 0009-9201
eISSN: 1532-5520
Grant note: R01 CA099908 / NCI NIH HHS P30 CA008748 / NCI NIH HHS R01 CA184101 / NCI NIH HHS
Language: English
Date published: 03/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiation Oncology; Obstetrics and Gynecology; Biochemistry and Molecular Biology; Chemical and Biochemical Engineering
Record Identifier: 9984197130102771

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