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Comparative DNA Methylation Profiling of Human and Murine ALK‐Positive B‐Cell Neoplasms

Title: Comparative DNA Methylation Profiling of Human and Murine ALK‐Positive B‐Cell Neoplasms
Authors: Glaser, Selina; Wagener, Rabea; Harkins, Shannon, K; Voena, Claudia; Bens, Susanne; Klapper, Wolfram; Laurent, Camille; Mathas, Stephan; Ren, Meiqi; Sander, Sandrine; Schnaudt‐mastrangelo, Charlotte; Wößmann, Wilhelm; Xerri, Luc; Ammerpohl, Ole; Zelenetz, Andrew, D; Louissaint, Abner; Chiarle, Roberto; Siebert, Reiner
Contributors: Universität Ulm - Ulm University Ulm, Allemagne; Universitätsklinikum Ulm - University Hospital of Ulm; Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel (CAU); Massachusetts General Hospital Boston; Harvard Medical School Boston (HMS); Università degli studi di Torino = University of Turin (UNITO); Service Anatomie et cytologie pathologiques CHU Toulouse; Pôle Biologie CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Centre de Recherches en Cancérologie de Toulouse (CRCT); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulouse (EPE UT); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse); Service Hématologie - IUCT-Oncopole CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Max Delbrück Center for Molecular Medicine Berlin (MDC); Helmholtz-Gemeinschaft = Helmholtz Association; Charité - UniversitätsMedizin = Berlin University Medicine; Humboldt-Universität zu Berlin = Humboldt University of Berlin = Université Humboldt de Berlin (HU Berlin); Experimental and Clinical Research Center; Charité and HELIOS-Klinikum; German Cancer Research Center - Deutsches Krebsforschungszentrum Heidelberg (DKFZ); University of Medicine Greifswald; Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf Hamburg (UKE); Aix Marseille Université (AMU); Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC); Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); German Center for Lung Research; German Center for Child and Adolescent Health Munich, Germany (DZKJ); Memorial Sloan Kettering Cancer Center (MSKCC); Boston Children's Hospital
Source: ISSN: 1045-2257.
Publisher Information: CCSD; Wiley
Publication Year: 2025
Collection: Université Toulouse III - Paul Sabatier: HAL-UPS
Subject Terms: ALK-positive LBCLs; DNA methylation; transgenic mouse model; [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]; [SDV]Life Sciences [q-bio]; [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Description: International audience ; Structural genomic variants leading to anaplastic lymphoma kinase (ALK) gene fusions and aberrant expression of the ALK tyrosine kinase are the hallmark of subtypes of T-and B-lineage neoplasms, namely ALK-positive anaplastic large lymphoma (ALCL) and ALK-positive large B-cell lymphoma (LBCL). The latter is a rare aggressive lymphoma, which has been initially identified as a variant of diffuse LBCL (DLBCL) with plasmablastic features. Here, we performed comparative DNA methylation profiling of human and murine ALK-positive B-cell neoplasms. Array-based DNA methylation data from ALK-positive LBCL samples of eight patients were compared to that of DLBCL (n = 75), multiple myeloma (MM, n = 24), ALK-positive ALCL (n = 12) and normal B-cell populations (n = 93). ALK-positive LBCLs share a distinct DNA methylation signature similar to that of MM, characterized by lower global DNA methylation levels compared to DLBCLs and normal B-cell populations. DNA methylation alterations in ALK-positive LBCL were predominantly located in heterochromatic and polycomb-repressed regions. The epigenetic age and relative proliferative history of ALK-positive LBCL were intermediate between MM and DLBCL. B-cell neoplasms in NPM::ALK transgenic mice showed a similar hypomethylated signature when compared to normal murine B cells. Cross-species comparison indicated conservation of chromatin states and pathways affected by hypomethylation. Together, the This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40879321; PUBMED: 40879321; PUBMEDCENTRAL: PMC12404666
DOI: 10.1002/gcc.70060
Availability: https://inserm.hal.science/inserm-05247424; https://inserm.hal.science/inserm-05247424v1/document; https://inserm.hal.science/inserm-05247424v1/file/Genes%20Chromosomes%20Cancer%20-%202025%20-%20Glaser%20-%20Comparative%20DNA%20Methylation%20Profiling%20of%20Human%20and%20Murine%20ALK%E2%80%90Positive%20B%E2%80%90Cell.pdf; https://doi.org/10.1002/gcc.70060
Rights: https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.33BBA198
Database: BASE