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Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age &lt;45 years,\n                    <jats:italic>HER2<\/jats:italic>\n                    amplification, and\n                    <jats:italic>GATA3<\/jats:italic>\n                    mutation are possible indicators of relapse.\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that\n                    <jats:italic>GATA3<\/jats:italic>\n                    dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-01959-9","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T06:03:08Z","timestamp":1617256988000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast"],"prefix":"10.1038","volume":"4","author":[{"given":"Satoi","family":"Nagasawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Kuze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-7287","authenticated-orcid":false,"given":"Ichiro","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Motoyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuguo","family":"Iwatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-7117","authenticated-orcid":false,"given":"Takamichi","family":"Yokoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junki","family":"Koike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Chosokabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2898-3550","authenticated-orcid":false,"given":"Manabu","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibiki","family":"Seino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Tsuchihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisuke","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Tsugawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4852-1879","authenticated-orcid":false,"given":"Yutaka","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"1959_CR1","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1093\/ajcp\/100.6.654","volume":"100","author":"RE Fechner","year":"1993","unstructured":"Fechner, R. 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