Open AccessCharacterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling
Author(s) -
Jianling Bi,
Kristina W. Thiel,
Jacob M. Litman,
Yuping Zhang,
Eric J. Devor,
A.M. Newtson,
Michael J. Schnieders,
Jesús González Bosquet,
Kimberly K. Leslie
Publication year - 2020
Publication title -
clinical obstetrics and gynecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.927
H-Index - 75
eISSN - 1532-5520
pISSN - 0009-9201
DOI - 10.1097/grf.0000000000000516
Subject(s) - organoid , medicine , ex vivo , histone deacetylase inhibitor , carcinosarcoma , ovarian cancer , cancer research , cancer , ovary , in vivo , histone deacetylase , pathology , computational biology , histone , microbiology and biotechnology , biology , carcinoma , genetics , gene
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.