Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype.

Autor:	Liffers ST; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Godfrey L; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Frohn L; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany., Haeberle L; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany., Yavas A; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany., Vesce R; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany., Goering W; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany., Opitz FV; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany., Stoecklein N; Department of General, Visceral and Pediatric Surgery, Heinrich-Heine-University and University Hospital of Dusseldorf, Dusseldorf, Germany., Knoefel WT; Department of General, Visceral and Pediatric Surgery, Heinrich-Heine-University and University Hospital of Dusseldorf, Dusseldorf, Germany., Schlitter AM; Institute of Pathology, Technische Universitaet Muenchen, Munich, Germany., Klöppel G; Institute of Pathology, Technische Universitaet Muenchen, Munich, Germany., Espinet E; HI-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH, Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Centre and DKFZ-ZMBH Alliance, Heidelberg, Germany.; German Cancer Consortium, (DKTK), Heidelberg, Germany., Trumpp A; HI-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH, Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Centre and DKFZ-ZMBH Alliance, Heidelberg, Germany.; German Cancer Consortium, (DKTK), Heidelberg, Germany., Siveke JT; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Esposito I; Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany Irene.Esposito@med.uni-duesseldorf.de.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2023 Mar; Vol. 72 (3), pp. 522-534. Date of Electronic Publication: 2022 Aug 09.
DOI:	10.1136/gutjnl-2021-326550
Abstrakt:	Objective: Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions. Design: Targeted and whole-genome low-coverage sequencing, genome-wide methylation and transcriptome analyses were applied on a final collective of 122 morphologically well-characterised low-grade and high-grade PDAC precursors, including intestinal and gastric intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasias (PanIN). Results: Epigenetic regulation of mucin genes determines the phenotype of PDAC precursors. PanIN and gastric IPMN display a ductal molecular profile and numerous similarly regulated pathways, including the Notch pathway, but can be distinguished by recurrent deletions and differential methylation and, in part, by the expression of mucin-like 3. Intestinal IPMN are clearly distinct lesions at the molecular level with a more instable genotype and are possibly related to a different ductal cell compartment. Conclusions: PDAC precursors with gastric and intestinal phenotype are heterogeneous in terms of morphology, genetic and epigenetic profile. This heterogeneity is related to a different cell identity and, possibly, to a different aetiology. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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