{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:49:21Z","timestamp":1790819361311,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004418","name":"Vrije Universiteit Brussel","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["VUB OZR SRP65"],"award-info":[{"award-number":["VUB OZR SRP65"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["2092"],"award-info":[{"award-number":["2092"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A \u2018classical\u2019 and a \u2018basal\u2010like\u2019 subtype of pancreatic cancer have been reported, with differential expression of\n                    <jats:italic>GATA6<\/jats:italic>\n                    and different dosages of mutant\n                    <jats:italic>KRAS<\/jats:italic>\n                    . We established\n                    <jats:italic>in situ<\/jats:italic>\n                    detection of\n                    <jats:italic>KRAS<\/jats:italic>\n                    point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin\u2010embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter\u2010patient and intra\u2010patient inter\u2010ductal heterogeneity, intraductal spatial phenotypes exist with anti\u2010correlating expression levels of\n                    <jats:italic>GATA6<\/jats:italic>\n                    and\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    . The basal\u2010like mRNA panel better captured the basal\u2010like cell states than widely used protein markers. The panels corroborated the co\u2010existence of the classical and basal\u2010like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial\u2010to\u2010mesenchymal transition respectively. Mutant\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    detection ascertained an epithelial origin of vimentin\u2010positive cells in the tumour. Uneven spatial distribution of cancer\u2010associated fibroblasts could recreate similar intra\u2010organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6212","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T07:10:42Z","timestamp":1697440242000},"page":"76-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["High\u2010resolution and quantitative spatial analysis reveal intra\u2010ductal phenotypic and functional diversification in pancreatic cancer"],"prefix":"10.1002","volume":"262","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1806-8372","authenticated-orcid":false,"given":"Ellis","family":"Michiels","sequence":"first","affiliation":[{"name":"Laboratory of Medical &amp; Molecular Oncology (LMMO) Vrije Universiteit Brussel (VUB)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9064-0225","authenticated-orcid":false,"given":"Hediel","family":"Madhloum","sequence":"additional","affiliation":[{"name":"Laboratory of Medical &amp; Molecular Oncology (LMMO) Vrije Universiteit Brussel (VUB)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5265-1134","authenticated-orcid":false,"given":"Silke","family":"Van Lint","sequence":"additional","affiliation":[{"name":"Laboratory of Medical &amp; Molecular Oncology (LMMO) Vrije Universiteit Brussel (VUB)  Brussels 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