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

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.

SUBMITTER: Bi J

PROVIDER: S-EPMC7521672 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Bi Jianling J Thiel Kristina W KW Litman Jacob M JM Zhang Yuping Y Devor Eric J EJ Newtson Andreea M AM Schnieders Michael J MJ Gonzalez Bosquet Jesus J Leslie Kimberly K KK

Clinical obstetrics and gynecology 20200301 1

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 ...[more]

PMID: 31876640

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