The consequence of oncomorphic TP53 mutations in ovarian cancer.
The consequence of oncomorphic TP53 mutations in ovarian cancer.
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DOI：
10.3390/ijms140919257
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发表时间：
2013-09-23
影响因子：
5.6
通讯作者：
Leslie KK
中科院分区：
文献类型：
--
作者：
Brachova P;Thiel KW;Leslie KK
卵巢癌是最致命的妇科恶性肿瘤，由于发现较晚和化疗耐药，其预后极差。最初，大多数肿瘤对化疗有反应，但最终由于耐药性的发展而复发。目前，没有生物标志物可以用来预测患者对化疗的反应。然而，很明显，肿瘤抑制基因 TP53 发生在 96% 的浆液性卵巢肿瘤中，它的突变改变了药物反应中涉及的核心分子途径。 TP53 突变的一种亚型，被广泛称为功能获得（GOF）突变，令人惊讶地将该蛋白从肿瘤抑制基因转变为癌基因。我们将由此产生的变化称为肿瘤形态。在这篇综述中，我们讨论了特定的 TP53 突变，包括由此产生的突变 p53 蛋白的已知肿瘤形态特性。例如，已报道了几种不同的肿瘤形态突变，但每种突变以不同的方式起作用，并对肿瘤进展和化疗耐药性具有不同的影响。为了为患有这种致命疾病的患者设计适当的药物干预措施，有必要了解每种突变改变的病理途径。
Ovarian cancer is the most lethal gynecological malignancy, with an alarmingly poor prognosis attributed to late detection and chemoresistance. Initially, most tumors respond to chemotherapy but eventually relapse due to the development of drug resistance. Currently, there are no biological markers that can be used to predict patient response to chemotherapy. However, it is clear that mutations in the tumor suppressor gene TP53, which occur in 96% of serous ovarian tumors, alter the core molecular pathways involved in drug response. One subtype of TP53 mutations, widely termed gain-of-function (GOF) mutations, surprisingly converts this protein from a tumor suppressor to an oncogene. We term the resulting change an oncomorphism. In this review, we discuss particular TP53 mutations, including known oncomorphic properties of the resulting mutant p53 proteins. For example, several different oncomorphic mutations have been reported, but each mutation acts in a distinct manner and has a different effect on tumor progression and chemoresistance. An understanding of the pathological pathways altered by each mutation is necessary in order to design appropriate drug interventions for patients suffering from this deadly disease.
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