Comparative DNA Methylation Profiling of Human and Murine ALK-Positive B-Cell Neoplasms Journal Article
| Authors: | Glaser, S.; Wagener, R.; Harkins, S. K.; Voena, C.; Bens, S.; Klapper, W.; Laurent, C.; Mathas, S.; Ren, M.; Sander, S. |
| Article Title: | Comparative DNA Methylation Profiling of Human and Murine ALK-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. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adolescent; adult; child; controlled study; human tissue; aged; human cell; nonhuman; cancer patient; mouse; animal tissue; multiple myeloma; animal experiment; animal model; cohort analysis; cell population; dna methylation; age; b lymphocyte; transgenic mouse; dna; chromatin; polycomb group protein; heterochromatin; anaplastic lymphoma kinase; medical history; cancer epigenetics; transgenic mouse model; species comparison; human; male; female; article; epigenetic age; alk-positive lbcls; alk-positive diffuse large b cell lymphoma |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 64 |
| Issue: | 7 |
| ISSN: | 10982264 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2025-01-01 |
| Start Page: | e70060 |
| Language: | English |
| DOI: | 10.1002/gcc.70060 |
| PROVIDER: | scopus |
| PMCID: | PMC12404666 |
| PUBMED: | 40879321 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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