The hydroxymethylome of multiple myeloma identifies FAM72D as a 1q21 marker linked to proliferation

Abstract : Cell identity relies on the cross-talk between genetics and epigenetics and their impact on gene expression. Oxidation of 5-methylcytosine into 5-hydroxymethylcytosine is the first step of an active DNA demethylation process occurring mainly at enhancers and gene bodies and, as such, participates in processes governing cell identity in normal and pathological conditions. Although genetic alterations are well documented in multiple myeloma, epigenetic alterations associated with this disease have not yet been thoroughly analyzed. To gain insight into the biology of multiple myeloma, genome-wide 5-hydroxymethylcytosine profiles were obtained and showed that regions enriched in this modified base overlap with multiple myeloma enhancers and super enhancers and are close to highly expressed genes. Through the definition of a multiple myeloma-specific 5-hydroxymethylcytosine signature, we identified FAM72D as a poor prognostic gene located on 1q21, a region amplified in high risk myeloma. We further uncovered that FAM72D functions as part of the FOXM1 transcription factor network controlling cell proliferation and survival and evidenced an increased sensitivity of cells expressing high levels of FOXM1 and FAM72 to epigenetic drugs targeting histone deacetylases and DNA methyltransferases.
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Fabrice Chatonnet, Amandine Pignarre, Aurelien Serandour, Gersende Caron, Stéphane Avner, et al.. The hydroxymethylome of multiple myeloma identifies FAM72D as a 1q21 marker linked to proliferation. Haematologica, Ferrata Storti Foundation, 2019, pp.haematol.2019.222133. ⟨10.3324/haematol.2019.222133⟩. ⟨hal-02165596⟩



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