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[http:\/\/wileyonlinelibrary.com\/onlineopen#OnlineOpen_Terms]"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Numerous studies have tested the association between\n                    <jats:italic>TP53<\/jats:italic>\n                    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\u2010grade 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\u2010grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations in HGPSC, we sequenced exons 2\u201311 and intron\u2013exon 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\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations were identified in 96.7% (\n                    <jats:italic>n<\/jats:italic>\n                    = 119\/123) of HGPSC cases. Molecular and pathological review of mutation\u2010negative cases showed evidence of p53 dysfunction associated with copy number gain of\n                    <jats:italic>MDM2<\/jats:italic>\n                    or\n                    <jats:italic>MDM4<\/jats:italic>\n                    , or indicated the exclusion of samples as being low\u2010grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation and progression\u2010free or overall survival was found. From this first comprehensive mapping of\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant\n                    <jats:italic>TP53<\/jats:italic>\n                    is a driver mutation in the pathogenesis of HGPSC cancers. Because\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright \u00a9 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2696","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T08:56:24Z","timestamp":1265187384000},"page":"49-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":699,"title":["Driver mutations in\n                    <i>TP53<\/i>\n                    are ubiquitous in high grade serous carcinoma of the ovary"],"prefix":"10.1002","volume":"221","author":[{"given":"Ahmed Ashour","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariush","family":"Etemadmoghadam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Temple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy 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