{"doi":"10.1002/gcc.70060","title":"Comparative <scp>DNA</scp> Methylation Profiling of Human and Murine <scp>ALK</scp>‐Positive B‐Cell Neoplasms","abstract":"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 findings suggest that in line with their phenotypical appearance human and murine ALK-positive B-cell lymphomas share an epigenetic profile more closely resembling that of plasma cell neoplasias than that of DLBCLs.","journal":"Genes Chromosomes and Cancer","year":2025,"id":570934,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE289985","GSE289988","GSE289990"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":14190,"name":"Rabea Wagener","orcid":"0000-0002-5394-0907","position":1,"is_corresponding":false},{"id":661832,"name":"Shannon Harkins","orcid":"0000-0002-7272-9197","position":2,"is_corresponding":false},{"id":665173,"name":"Claudia Voena","orcid":"0000-0002-1324-1431","position":3,"is_corresponding":false},{"id":733737,"name":"Susanne Bens","orcid":"0009-0008-5263-495X","position":4,"is_corresponding":false},{"id":13664,"name":"Wolfram Klapper","orcid":"0000-0001-7208-4117","position":5,"is_corresponding":false},{"id":838695,"name":"Camille Laurent","orcid":"0000-0002-5375-7512","position":6,"is_corresponding":false},{"id":1034661,"name":"Stephan Mathas","orcid":"0000-0001-9626-1413","position":7,"is_corresponding":false},{"id":1476800,"name":"Meiqi Ren","orcid":null,"position":8,"is_corresponding":false},{"id":470976,"name":"Sandrine Sander","orcid":"0000-0003-4645-3366","position":9,"is_corresponding":false},{"id":1476801,"name":"Charlotte Schnaudt‐Mastrangelo","orcid":null,"position":10,"is_corresponding":false},{"id":1476395,"name":"Wilhelm Woessmann","orcid":"0000-0002-6315-0888","position":11,"is_corresponding":false},{"id":1184264,"name":"Luc Xerri","orcid":"0000-0002-8672-9921","position":12,"is_corresponding":false},{"id":13207,"name":"Ole Ammerpohl","orcid":"0000-0003-3539-2326","position":13,"is_corresponding":false},{"id":233551,"name":"Andrew D. Zelenetz","orcid":"0000-0003-1403-6883","position":14,"is_corresponding":false},{"id":251430,"name":"Abner Louissaint","orcid":"0000-0001-6707-917X","position":15,"is_corresponding":false},{"id":42115,"name":"Roberto Chiarle","orcid":"0000-0003-1564-8531","position":16,"is_corresponding":false},{"id":228583,"name":"Reiner Siebert","orcid":"0000-0002-6492-5323","position":17,"is_corresponding":false},{"id":868398,"name":"Selina Glaser","orcid":null,"position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40879321","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}