Characterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling.
Characterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling.
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DOI：
10.1097/grf.0000000000000516
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发表时间：
2020-03
影响因子：
1.5
通讯作者：
Leslie KK
中科院分区：
文献类型：
--
作者：
Bi J;Thiel KW;Litman JM;Zhang Y;Devor EJ;Newtson AM;Schnieders MJ;Gonzalez Bosquet J;Leslie KK
在我们对1例IIIC期卵巢癌肉瘤患者的概念验证研究中，我们发现了肿瘤抑制基因TP53的一种罕见突变，导致N131缺失。类器官培养物的免疫荧光成像显示p53蛋白过度染色。计算模型表明，这个残基是重要的，以维持蛋白质的构象。药物筛选确定了蛋白酶体抑制剂与组蛋白脱乙酰酶抑制剂的组合作为最有效的治疗。这些数据为成功培养患者肿瘤和离体分析药物反应提供了证据
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