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Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field of mutant cells that is predisposed towards lesion formation. To study the clonal and spatial relationships between morphologically normal breast epithelium adjacent to pre\u2010cancerous lesions, we developed a three\u2010dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival, formalin\u2010fixed breast tissue with the non\u2010obligate breast cancer precursor ductal carcinoma <jats:italic>in situ<\/jats:italic> (DCIS). Using this 3D image\u2010guided characterization method, we built high\u2010resolution spatial maps of DNA copy number aberration (CNA) profiles within the DCIS lesion and the surrounding normal mammary ducts. We show that the local heterogeneity within a DCIS lesion is limited. 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Together, our study indicates that pre\u2010malignant breast transformations frequently develop within mutant clonal fields of morphologically normal\u2010looking ducts. \u00a9 2024 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6289","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T05:00:15Z","timestamp":1716440415000},"page":"360-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ductal carcinoma <i>in situ<\/i> develops within clonal fields of mutant cells in morphologically normal ducts"],"prefix":"10.1002","volume":"263","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-8392","authenticated-orcid":false,"given":"Stefan J","family":"Hutten","sequence":"first","affiliation":[{"name":"Division of Molecular 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