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Onc."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dual pancreatic cancers, either synchronous or metachronous in presentation, are a rare occurrence. It remains unclear if these lesions are clonally related or independently occurring primary malignancies. Herein we present a cohort (N\u2009=\u200922) with dual pancreatic ductal adenocarcinoma (PDAC) tumors to resolve previously conflicting reports and interrogate the underlying biological and clinical characteristics of this patient population. Next-generation sequencing of paired lesions (N\u2009=\u200910) revealed that while most dual PDAC are clonally related, independently occurring lesions do occur, irrespective of the interval between lesions. Integrated clinical, genomic, and histopathological analyses revealed a high frequency of lymph node-negative, intraductal papillary mucinous neoplasm (IPMN)-associated cancers,\n                    <jats:italic>KRAS<\/jats:italic>\n                    and\/or\n                    <jats:italic>SMAD4<\/jats:italic>\n                    wild-type tumors, and classical subtype by immunohistochemistry, all collectively associated with more favorable outcomes. Acknowledging the highly selected nature of this cohort, isolated intrapancreatic metastases demonstrate a more indolent biology and these patients may benefit from personalized management approaches beyond traditional paradigms.\n                  <\/jats:p>","DOI":"10.1038\/s41698-026-01313-4","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:45:48Z","timestamp":1770507948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual pancreatic carcinomas: clonally related or independent primaries?"],"prefix":"10.1038","volume":"10","author":[{"given":"Joshua D.","family":"Schoenfeld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vignesh","family":"Ravichandran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeynep","family":"Tarcan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hulya","family":"Sahin-Ozkan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison L.","family":"Richards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadeem","family":"Bilani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne F.","family":"Chou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine A.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"McManamon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Varghese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fergus","family":"Keane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael I.","family":"D\u2019Angelica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Jarnagin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Drebin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Reidy-Lagunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice C.","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sree B.","family":"Chalasani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiyinfolu","family":"Balogun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wungki","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth H.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Soares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T. 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D.R.L. is on the scientific advisory board for Exelexis, Novartis, and Wren Laboratories; received research support from Novartis, Merck. Z.K.S has intellectual property rights in SOPHiA Genetics and serves as an Associate Editor for JCO Precision Oncology and as a Section Editor for UpToDate. Z.K.S immediate family member serves on the Board of Directors for Adverum Biotechnologies, is Co-Founder, CMO and President for Blue Gen Therapeutics Foundation, and serves as a consultant in Ophthalmology for Apellis, Novartis, Outlook Therapeutics, Optos, and Regeneron outside the submitted work. E.M.O has received research funding from Genentech\/Roche, BioNTech, AstraZeneca, Arcus, Elicio, Parker Institute, NIH\/NCI, Digestive Care, Break Through Cancer, Agenus, Amgen, and Revolution Medicines; consulted (mostly uncompensated) for Arcus, AstraZeneca, Ability Pharma, Alligator BioSciences, Agenus, BioNTech, Ipsen, Ikena, Merck, Moma Therapeutics, Novartis, Leap Therapeutics, Astellas, BMS, Revolution Medicines, Regeneron, and Tango; received travel support from BioNTech and Arcus; other support from American Association of Cancer Research (AACR), American Society of Clinical Oncology (ASCO), Imedex, Research To Practice, and Stand Up to Cancer (SU2C); and her spouse has received support from AbbVie. All other authors declare no potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"112"}}