{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:47:15Z","timestamp":1789094835798,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T00:00:00Z","timestamp":1442793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"European Research Council (ERC advanced 2012-AdG, Mass-Care)","award":["322986"],"award-info":[{"award-number":["322986"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Somatic mutations in cervical intraepithelial neoplasia (CIN) are largely unknown. Here, we profiled 35 cervical carcinomas and 23 CIN grade 2\/3 (CIN2\/3) for mutations in 48 cancer\u2010related genes using a Next Generation Sequencing\u2010based cancer panel. <jats:italic>PIK3CA<\/jats:italic> exon 9 was the most frequently mutated locus in cervical carcinoma and the only mutated locus detected in CIN2\/3. These <jats:italic>PIK3CA<\/jats:italic> exon 9 mutation findings were verified in a large, independent series (<jats:italic>n<\/jats:italic>\u2009=\u2009647) covering all stages of cervical carcinogenesis using high resolution melting\u2010guided Sanger sequencing. <jats:italic>PIK3CA<\/jats:italic> exon 9 mutation frequency was 37.1% (13\/35; 95%CI 21.2\u201354.0%) in cervical carcinoma, and 2.4% (5\/209; 95%CI 0.5\u20134.7%) in CIN3. No <jats:italic>PIK3CA<\/jats:italic> exon 9 mutations were detected in CIN2 (0\/144), CIN1 (0\/154) and normal cervix (0\/105). In a third series of 46 CIN2\/3 lesions from women with a known 5\u2010year history of preceding high\u2010risk human papillomavirus (hrHPV) infection, detection of <jats:italic>PIK3CA<\/jats:italic> exon 9 mutation was confined to 2 (5.4%; 95%CI 0.0\u201313.2%) CIN3 lesions with preceding hrHPV infection \u22655 years, and was absent in those with a short duration (&lt;5 years) of preceding hrHPV infection. In conclusion, somatic mutation in <jats:italic>PIK3CA<\/jats:italic> represents a late event during cervical carcinogenesis, detected in a substantial subset of cervical carcinoma, but only in a minority of CIN3.<\/jats:p>","DOI":"10.1002\/cjp2.27","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T05:02:47Z","timestamp":1442811767000},"page":"207-211","source":"Crossref","is-referenced-by-count":32,"title":["Somatic mutation in <i>PIK3CA<\/i> is a late event in cervical carcinogenesis"],"prefix":"10.1002","volume":"1","author":[{"given":"Wina","family":"Verlaat","sequence":"first","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter JF","family":"Snijders","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinda IH","family":"van Moorsel","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"Bleeker","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Rozendaal","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoud","family":"Sie","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bauke","family":"Ylstra","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris JLM","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renske DM","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle AM","family":"Heideman","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The 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