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Onc."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genomic alterations in fibroblast growth factor receptor (<jats:italic>FGFR)<\/jats:italic> genes are present in a small number of metastatic pancreatic ductal adenocarcinomas (PDAC) and may represent an emerging subgroup of patients likely to benefit from FGFR targeted therapies. Here we present four <jats:italic>FGFR2<\/jats:italic> fusion-positive metastatic PDAC patients who exhibited durable responses or disease control to FGFR kinase inhibitors. Utilizing our custom <jats:italic>FGFR<\/jats:italic> focused cell-free DNA assay, FGFR-Dx, we serially monitored variant allele fractions of <jats:italic>FGFR2<\/jats:italic> fusions during FGFR inhibitor treatment and observed dynamic changes correlating with clinical responses. Genomic analysis of 30,229 comprehensively profiled pancreatic cancers revealed <jats:italic>FGFR1-3<\/jats:italic> fusions in 245 cases, an incidence of 0.81%. <jats:italic>FGFR<\/jats:italic> fusions were generally mutually exclusive from other known oncogenes. Our findings provide clinical evidence for identifying and treating <jats:italic>FGFR2<\/jats:italic> fusion-positive PDAC patients with FGFR targeted therapy.<\/jats:p>","DOI":"10.1038\/s41698-024-00683-x","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T11:21:37Z","timestamp":1726744897000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["FGFR2-fusions define a clinically actionable molecular subset of pancreatic cancer"],"prefix":"10.1038","volume":"8","author":[{"given":"Leah","family":"Stein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2275-1126","authenticated-orcid":false,"given":"Karthikeyan","family":"Murugesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie W.","family":"Reeser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Risch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9688-0396","authenticated-orcid":false,"given":"Michele R.","family":"Wing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoosha","family":"Paruchuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Samorodnitsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Hoskins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy","family":"Dao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dat","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Babcook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Seok","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Avenarius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Imam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aharon G.","family":"Freud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-3038","authenticated-orcid":false,"given":"Sameek","family":"Roychowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"683_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72, 7\u201333 (2022).","journal-title":"CA Cancer J. Clin."},{"key":"683_CR2","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","volume":"364","author":"T Conroy","year":"2011","unstructured":"Conroy, T. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 364, 1817\u20131825 (2011).","journal-title":"N. Engl. J. Med."},{"key":"683_CR3","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","volume":"369","author":"DD Von Hoff","year":"2013","unstructured":"Von Hoff, D. D. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 369, 1691\u20131703 (2013).","journal-title":"N. Engl. J. 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(2017), QED Therapeutics (2018, 2019), Bayer (2020). [Health care companies) (<10,000 USD). S.R. received honoraria from IDT Integrated DNA Technologies (2017), Illumina (2018). [Technology companies]. S.R. received consulting fees from QED Therapeutics (2018, 2019) and Merck (2019). [Health care companies] (<10,000 USD). S.R. received travel reimbursement from Incyte Corporation (2019) (Less than 999 USD). K.M. employed by Foundation Medicine, Cambridge, MA, USA and holds stocks or shares from Roche Holdings AG. M.B. holds stock interests in Applied Materials, Incyte, Pfizer, and Thermo Fisher Scientific. Z.R. holds stocks or shares from Alnylam Pharmaceuticals, Geron Corporations, Lineage Cell Therapeutic, Oncolytics Biotech, Pfizer Inc., Repligen Corporation, Sangamo Therapeutics, and Viatris Inc.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"207"}}