DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple my
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RESEARCH
DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma Jean‑Baptiste Alberge1,2, Florence Magrangeas1,2,3, Mirko Wagner4, Soline Denié1, Catherine Guérin‑Charbonnel1,2,5, Loïc Campion1,2,5, Michel Attal6,7, Hervé Avet‑Loiseau6,7, Thomas Carell4, Philippe Moreau1,2,3, Stéphane Minvielle1,2,3* and Aurélien A. Sérandour1,8*
Abstract Background: Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play a role in tumor biology; however, little is known about its level and distribution in myeloma. In this study, we investigated the global level and the genomic localization of 5hmC in myeloma cells from 40 newly diagnosed patients, including paired relapses, and of control individuals. Results: Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P
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