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We recently investigated the genomic landscape of early\u2010 and late\u2010stage HGSC and found higher ploidy in late\u2010stage (median 3.1) than early\u2010stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole\u2010genome duplication (WGD) observed in late\u2010stage disease were determined early in the evolution of HGSC, we analysed archival formalin\u2010fixed paraffin\u2010embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser\u2010capture microdissected and sequenced using shallow whole\u2010genome sequencing (sWGS), while invasive ovarian\/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next\u2010generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian\/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. \u00a9 2024 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6322","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T23:50:26Z","timestamp":1719964226000},"page":"42-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The genomic trajectory of ovarian high\u2010grade serous carcinoma can be observed in\n                    <scp>STIC<\/scp>\n                    lesions"],"prefix":"10.1002","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-240X","authenticated-orcid":false,"given":"Zhao","family":"Cheng","sequence":"first","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer Imperial College London  London UK"},{"name":"Cancer Research UK Cambridge Institute University of Cambridge, Li Ka Shing Centre  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5260-3506","authenticated-orcid":false,"given":"Darren P","family":"Ennis","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Action Research Centre, Department of Surgery and Cancer Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0606-5150","authenticated-orcid":false,"given":"Bingxin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cell and 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