{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:26:53Z","timestamp":1789684013613,"version":"4.0.1"},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Malignant phyllodes tumors (MPTs) are rare fibroepithelial tumors of the breast with aggressive biologic behavior and high recurrence rates. Surgery remains the primary treatment modality for these tumors; however, initial investigations suggest a potential for targeted therapies in managing this disease. Therefore, we aimed to assess the molecular landscape of MPTs to reveal possible treatment opportunities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              MPTs (n = 57) from primary and metastatic sites underwent genomic sequencing (592-gene panel or whole exome), whole-transcriptome sequencing, and immunohistochemistry (PD-L1, human epidermal growth factor receptor 2 [HER2]) at Caris Life Sciences (Phoenix, AZ). Immune cell fractions in the tumor microenvironment were estimated using quanTIseq. Mann-Whitney\n              <jats:italic>U<\/jats:italic>\n              , chi-square, and Fisher\u2019s exact tests were used to determine significance (\n              <jats:italic>P<\/jats:italic>\n              &lt; .05).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              MPTs had low\n              <jats:italic>ERBB2<\/jats:italic>\n              expression, comparable with the HER2-negative subset of a large cohort of breast adenocarcinoma samples (N = 9,926). Frequent alterations included\n              <jats:italic>TERT<\/jats:italic>\n              promoter;\n              <jats:italic>MED12<\/jats:italic>\n              ,\n              <jats:italic>TP53<\/jats:italic>\n              , and\n              <jats:italic>NF1<\/jats:italic>\n              mutations; and less frequently\n              <jats:italic>EGFR<\/jats:italic>\n              ,\n              <jats:italic>PIK3CA<\/jats:italic>\n              , and\n              <jats:italic>BRAF<\/jats:italic>\n              . Differences in mutation prevalences were observed between primary sites, lung metastases, and nonlung metastases. One MPT specimen harbored a pathogenic\n              <jats:italic>TPM4:NTRK1<\/jats:italic>\n              fusion, and treatment with larotrectinib for over 16 months suggested a clinical response to therapy. PD-L1+ status was observed in 15.2% of MPTs overall, with similar prevalence in primary sites and lung metastases. B cells, M2 macrophages, neutrophils, and natural killer cells had the highest median cell fractions in MPTs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              Considering the occurrence of several actionable alterations including a\n              <jats:italic>TPM4:NTRK1<\/jats:italic>\n              fusion reported herein, these results support the use of next-generation sequencing (NGS) including RNA analysis for fusion detection to identify such alterations in patients with MPTs. These findings highlight the importance of comprehensive NGS in MPT research to uncover potential targeted treatment options for these patients.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po.24.00289","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T20:59:29Z","timestamp":1733432369000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-4692","authenticated-orcid":true,"given":"Rani","family":"Bansal","sequence":"first","affiliation":[{"name":"Duke Cancer Institute, Duke University Hospital, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolulope","family":"Adeyelu","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, 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GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-2513","authenticated-orcid":true,"given":"Matthew J.","family":"Oberley","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-1722","authenticated-orcid":true,"given":"Stephanie L.","family":"Graff","sequence":"additional","affiliation":[{"name":"Legorreta Cancer Center at Brown University, Providence, RI"},{"name":"Lifespan Cancer Institute, Providence, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-0775","authenticated-orcid":true,"suffix":"Jr","given":"George W.","family":"Sledge","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, 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