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http://hdl.handle.net/1942/41804
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DC Field | Value | Language |
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dc.contributor.author | Michiels, Ellis | - |
dc.contributor.author | Madhloum, Hediel | - |
dc.contributor.author | Van Lint, Silke | - |
dc.contributor.author | Messaoudi, Nouredin | - |
dc.contributor.author | Kunda, Rastislav | - |
dc.contributor.author | MARTENS, Sandrina | - |
dc.contributor.author | Giron, Philippe | - |
dc.contributor.author | Olsen, Catharina | - |
dc.contributor.author | Lefesvre, Pierre | - |
dc.contributor.author | Dusetti, Nelson | - |
dc.date.accessioned | 2023-11-15T13:41:29Z | - |
dc.date.available | 2023-11-15T13:41:29Z | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-11-15T13:34:12Z | - |
dc.identifier.citation | JOURNAL OF PATHOLOGY, 262 (1), p. 76-89 | - |
dc.identifier.uri | http://hdl.handle.net/1942/41804 | - |
dc.description.abstract | A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRAS(G12D). The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRAS(G12D) detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. (c) 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. | - |
dc.description.sponsorship | We are grateful for the service provided by Visual and Spatial Tissue Analysis (https://vsta.research.vub.be). We also thank Lien Willems for her help with quantification and figure design. Funding: Laboratory work in LMMO was supported by Stichting tegen Kanker Translational & Clinical Research Grants 2018 #2092 and by VUB OZR SRP65. IR is a recipient of an Odysseus I fellowship of the Research Foundation-Flanders (G0F8916N). EM was financially supported by Innoser NV and Flanders Innovation & Entrepreneurship (VLAIO). | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.rights | 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made | - |
dc.subject.other | molecular heterogeneity | - |
dc.subject.other | mutation detection | - |
dc.subject.other | spatial subtyping | - |
dc.subject.other | pancreatic cancer | - |
dc.subject.other | plasticity | - |
dc.title | High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 89 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 76 | - |
dc.identifier.volume | 262 | - |
local.format.pages | 14 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Rooman, I (corresponding author), Vrije Univ Brussel, Laarbeeklaan 103, B-1090 Jette, Brussels, Belgium. | - |
dc.description.notes | ilse.rooman@vub.be | - |
local.publisher.place | 111 RIVER ST, HOBOKEN 07030-5774, NJ USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1002/path.6212 | - |
dc.identifier.isi | 001089263800001 | - |
dc.contributor.orcid | Martens, Sandrina/0000-0003-3421-2581; Dusetti, | - |
dc.contributor.orcid | Nelson/0000-0002-6161-8483; Giron, Philippe/0000-0002-1331-1890; | - |
dc.contributor.orcid | Messaoudi, Nouredin/0000-0003-2799-2604 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Michiels, Ellis; Madhloum, Hediel; Van Lint, Silke; Martens, Sandrina; Rooman, Ilse] Vrije Univ Brussel VUB, Lab Med & Mol Oncol LMMO, Brussels, Belgium. | - |
local.description.affiliation | [Messaoudi, Nouredin; Kunda, Rastislav; Ahsayni, Farah] Vrije Univ Brussel VUB, Univ Ziekenhuis Brussel UZB, Dept Surg, Dept Gastroenterol Hepatol,Dept Advanced Intervent, Brussels, Belgium. | - |
local.description.affiliation | [Martens, Sandrina] Hasselt Univ, Biomed Res Inst, Dept Cardio & Organ Syst, Diepenbeek, Belgium. | - |
local.description.affiliation | [Giron, Philippe; Olsen, Catharina] Vrije Univ Brussel VUB, Univ Ziekenhuis Brussel UZB, Ctr Med Genet, Clin Sci Reproduct & Genet Res Grp, Brussels, Belgium. | - |
local.description.affiliation | [Lefesvre, Pierre] Univ Ziekenhuis Brussel UZB, Dept Anatomo Pathol, Brussels, Belgium. | - |
local.description.affiliation | [Dusetti, Nelson; EL Mohajer, Leila; Tomasini, Richard] Marseille Univ, CNRS, INSERM, Canc Res Ctr Marseille CRCM,Inst Paoli Calmettes, Marseille, France. | - |
local.description.affiliation | [Hawinkels, Lukas J. A. C.] Leiden Univ Med Ctr LUMC, Dept Gastroenterol & Hepatol, Leiden, Netherlands. | - |
local.description.affiliation | [Nicolle, Remy] Ctr Rech inflammat CRI, INSERM, Paris, France. | - |
local.description.affiliation | [Arsenijevic, Tatjana; Van Laethem, Jean-Luc] Univ Libre Bruxelles ULB, Fac Med, Lab Expt Gastroenterol, Brussels, Belgium. | - |
local.description.affiliation | [Arsenijevic, Tatjana; Van Laethem, Jean-Luc] Univ Libre Bruxelles, HUB Bordet Erasme Hosp, Dept Gastroenterol Hepatol & Digest Oncol, Brussels, Belgium. | - |
local.description.affiliation | [Bouchart, Christelle] Univ Libre Bruxelles ULB, Hosp Univ Bruxelles HUB, Inst Jules Bordet, Dept Radiat Oncol, Brussels, Belgium. | - |
local.description.affiliation | [Rooman, Ilse] Vrije Univ Brussel, Laarbeeklaan 103, B-1090 Jette, Brussels, Belgium. | - |
local.uhasselt.international | yes | - |
item.fullcitation | Michiels, Ellis; Madhloum, Hediel; Van Lint, Silke; Messaoudi, Nouredin; Kunda, Rastislav; MARTENS, Sandrina; Giron, Philippe; Olsen, Catharina; Lefesvre, Pierre & Dusetti, Nelson (2023) High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer. In: JOURNAL OF PATHOLOGY, 262 (1), p. 76-89. | - |
item.contributor | Michiels, Ellis | - |
item.contributor | Madhloum, Hediel | - |
item.contributor | Van Lint, Silke | - |
item.contributor | Messaoudi, Nouredin | - |
item.contributor | Kunda, Rastislav | - |
item.contributor | MARTENS, Sandrina | - |
item.contributor | Giron, Philippe | - |
item.contributor | Olsen, Catharina | - |
item.contributor | Lefesvre, Pierre | - |
item.contributor | Dusetti, Nelson | - |
item.fulltext | With Fulltext | - |
item.accessRights | Open Access | - |
crisitem.journal.issn | 0022-3417 | - |
crisitem.journal.eissn | 1096-9896 | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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The Journal of Pathology - 2023 - Michiels - High‐resolution and quantitative spatial analysis reveal intra‐ductal.pdf | Published version | 13.28 MB | Adobe PDF | View/Open |
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