{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:09:56Z","timestamp":1754161796255,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1074","SFB1530"],"award-info":[{"award-number":["SFB1074","SFB1530"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA196703\u201001"],"award-info":[{"award-number":["R01 CA196703\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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\u2010 and B\u2010lineage neoplasms, namely ALK\u2010positive anaplastic large lymphoma (ALCL) and ALK\u2010positive large B\u2010cell 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\u2010positive B\u2010cell neoplasms. Array\u2010based DNA methylation data from ALK\u2010positive LBCL samples of eight patients were compared to that of DLBCL (<jats:italic>n<\/jats:italic>\u2009=\u200975), multiple myeloma (MM, <jats:italic>n<\/jats:italic>\u2009=\u200924), ALK\u2010positive ALCL (<jats:italic>n<\/jats:italic>\u2009=\u200912) and normal B\u2010cell populations (<jats:italic>n<\/jats:italic>\u2009=\u200993). ALK\u2010positive 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\u2010cell populations. DNA methylation alterations in ALK\u2010positive LBCL were predominantly located in heterochromatic and polycomb\u2010repressed regions. The epigenetic age and relative proliferative history of ALK\u2010positive LBCL were intermediate between MM and DLBCL. B\u2010cell neoplasms in <jats:italic>NPM<\/jats:italic>::<jats:italic>ALK<\/jats:italic> transgenic mice showed a similar hypomethylated signature when compared to normal murine B cells. Cross\u2010species comparison indicated conservation of chromatin states and pathways affected by hypomethylation. Together, the findings suggest that in line with their phenotypical appearance human and murine ALK\u2010positive B\u2010cell lymphomas share an epigenetic profile more closely resembling that of plasma cell neoplasias than that of DLBCLs.<\/jats:p>","DOI":"10.1002\/gcc.70060","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T09:49:48Z","timestamp":1753523388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative <scp>DNA<\/scp> Methylation Profiling of Human and Murine <scp>ALK<\/scp>\u2010Positive B\u2010Cell Neoplasms"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2923-1829","authenticated-orcid":false,"given":"Selina","family":"Glaser","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Ulm University and Ulm University Medical Center  Ulm 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and Ulm University Medical Center  Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-4117","authenticated-orcid":false,"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Institute of Pathology Christian\u2010Albrechts\u2010University  Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Laurent","sequence":"additional","affiliation":[{"name":"Department of Pathology Institut Universitaire du Cancer de Toulouse\u2010Oncopole, and Laboratoire d'Excellence Toulouse Cancer, Centre de Recherche en Canc\u00e9rologie de Toulouse INSERM U1037  Toulouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Mathas","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association (MDC), Group Biology of Malignant Lymphomas  Berlin Germany"},{"name":"Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Hematology, Oncology and Tumor Immunology Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t Zu Berlin  Berlin Germany"},{"name":"Experimental and Clinical Research Center (ECRC), a Joint Cooperation Between the MDC and the Charit\u00e9  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiqi","family":"Ren","sequence":"additional","affiliation":[{"name":"Division Adaptive Immunity and Lymphoma German Cancer Research Center (DKFZ) Heidelberg  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Sander","sequence":"additional","affiliation":[{"name":"Division Adaptive Immunity and Lymphoma German Cancer Research Center (DKFZ) Heidelberg  Heidelberg Germany"},{"name":"Comprehensive Cancer Center (CCC) Mecklenburg\u2010Vorpommern, University Medicine Greifswald  Greifswald Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Schnaudt\u2010Mastrangelo","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Ulm University and Ulm University Medical Center  Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6315-0888","authenticated-orcid":false,"given":"Wilhelm","family":"W\u00f6\u00dfmann","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology and NHL\u2010BFM Study Center Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Xerri","sequence":"additional","affiliation":[{"name":"Department of Pathology Institut Paoli\u2010Calmettes, Centre de Recherche en Canc\u00e9rologie de Marseille, Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Ammerpohl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Ulm University and Ulm University Medical Center  Ulm Germany"},{"name":"Institute of Human Genetics Christian\u2010Albrechts\u2010University Kiel  Kiel Germany"},{"name":"Airway Research Center North, Member of the German Center for Lung Research (DZL)  Grosshansdorf Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Ulm  Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Zelenetz","sequence":"additional","affiliation":[{"name":"Lymphoma Service, Department of Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Abner","family":"Louissaint","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General 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