{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:10:51Z","timestamp":1788858651606,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Background<\/jats:title>\n \n Malignant phyllodes tumours (MPT) are aggressive breast fibroepithelial neoplasms. Their rarity has limited their genetic characterization, and associations with genetic ancestry and progression drivers remain poorly understood. Prior studies suggest two evolutionary pathways according to\n MED12<\/jats:italic>\n mutational status. We sought to determine the repertoire of somatic genetic alterations in cancer genes in primary versus metastatic\/recurrent MPTs, and according to\n MED12<\/jats:italic>\n mutational status and genetic ancestry.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n We analysed the paired tumour\u2010normal targeting sequencing data (up to 505 cancer\u2010related genes) of 31 MPTs (primary,\n n<\/jats:italic>\n \u2009=\u200920; metastatic\/recurrent,\n n<\/jats:italic>\n \u2009=\u200911).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Metastatic\/recurrent MPTs harboured a numerically higher frequency of genetic alterations in\n CDKN2A\/2B<\/jats:italic>\n (55% vs. 25%). Moreover, analysis of an MPT case with paired primary and metastatic samples revealed a\n CDKN2A\/2B<\/jats:italic>\n homozygous deletion restricted to the metastatic sample, suggesting a role for\n CDKN2A\/2B<\/jats:italic>\n in progression. Compared with\n MED12<\/jats:italic>\n \u2010wild type MPTs,\n MED12<\/jats:italic>\n \u2010mutant MPTs had higher tumour mutation burden (\n P<\/jats:italic>\n \u2009=\u20090.002), frequency of\n TERT<\/jats:italic>\n promoter (82% vs. 35%;\n P<\/jats:italic>\n \u2009=\u20090.02) and\n RB1<\/jats:italic>\n mutations (45% vs. 5%;\n P<\/jats:italic>\n \u2009=\u20090.01). Genetic alterations in the PI3K pathway, including\n PIK3CA<\/jats:italic>\n and\n PTEN<\/jats:italic>\n , were only present in\n MED12<\/jats:italic>\n \u2010wild type MPTs, and absent in\n MED12<\/jats:italic>\n \u2010mutant cases (15% vs. 0%;\n P<\/jats:italic>\n \u2009>\u20090.05). Furthermore, genetic alterations in\n EGFR<\/jats:italic>\n were restricted to MPTs from patients of European genetic ancestry and absent in those of Asian ancestry (43% vs. 0%;\n P<\/jats:italic>\n \u2009>\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Taken together, the repertoire of genetic alterations in primary and metastatic\/recurrent MPTs shows overlap, and\n CDKN2A\/2B<\/jats:italic>\n homozygous deletions may play a role in progression. Additionally, molecular profiles of MPTs may vary according to genetic ancestry and\n MED12<\/jats:italic>\n mutational status.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.70197","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:47:26Z","timestamp":1780537646000},"page":"603-613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Landscape of genetic alterations affecting cancer genes in primary and advanced malignant phyllodes tumours"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-561X","authenticated-orcid":false,"given":"Selma","family":"Yeni Yildirim","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5007-2964","authenticated-orcid":false,"given":"Lounes","family":"Djerroudi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York USA"},{"name":"Department of Pathology, Institut Curie Institute of Women's Cancers Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4677-9398","authenticated-orcid":false,"given":"Dara","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-8468","authenticated-orcid":false,"given":"Edi","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9927-1270","authenticated-orcid":false,"given":"Britta","family":"Weigelt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-8049","authenticated-orcid":false,"given":"Fresia","family":"Pareja","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"WHO classification of Tumours editorial board breast tumours","author":"Thike 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