Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.
Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.
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DOI：
10.1002/path.2696
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发表时间：
2010-05
影响因子：
7.3
通讯作者：
Brenton, James D.
中科院分区：
文献类型：
--
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
关键词：
许多研究已经测试了卵巢癌中TP53突变与预后之间的关联，但这些研究一直被研究设计，方法论和/或异质性的局限性混淆。卵巢癌的组织学亚型。癌（HGPSC）。 IV。令人惊讶的是，在HGPSC病例的96.7％（n = 119/123）中发现了致病性TP53突变。显示了与MDM2或MDM4的拷贝数增益相关的p53功能障碍，或者表明样品是低级浆液性肿瘤或不确定原发性的癌从均匀的组中发现了TP53突变和无进展或总生存率。 HGPSC患者，我们包括突变的TP53是HGPSC癌症的驱动器突变，因为TP53突变几乎总是在HGPSC中呈现。由约翰·威利（John Wiley＆Sons）有限公司出版。
Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these have been consistently confounded by limitations in study design, methodology, and/or heterogeneity in the sample cohort. High-grade serous (HGS) carcinoma is the most clinically important histological subtype of ovarian cancer. As these tumours may arise from the ovary, Fallopian tube or peritoneum, they are collectively referred to as high-grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of TP53 mutations in HGPSC, we sequenced exons 2–11 and intron–exon boundaries in tumour DNA from 145 patients. HGPSC cases were defined as having histological grade 2 or 3 and FIGO stage III or IV. Surprisingly, pathogenic TP53 mutations were identified in 96.7% (n = 119/123) of HGPSC cases. Molecular and pathological review of mutation-negative cases showed evidence of p53 dysfunction associated with copy number gain of MDM2 or MDM4, or indicated the exclusion of samples as being low-grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between TP53 mutation and progression-free or overall survival was found. From this first comprehensive mapping of TP53 mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers. Because TP53 mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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