DNA METHYLATION IN MULTIPLE MYELOMA
Carvalho F.1, Okuda EA1, Felix RS2, Almeida MSS2, Andrade VCC2, Yamamoto M2, Zago MA3, Colleoni GWB2, Vettore AL1.
1Ludwig Institute for Cancer Research, Sao Paulo Branch, Brazil; 2Discipline of Hematology and Hemotherapy UNIFESP/EPM, Brazil.; 3Faculdade de Medicina de Ribeirão Preto/USP, Brazil
Introduction: Multiple Myeloma (MM) is characterized by neoplasic proliferation of monoclonal plasma cells. These neoplasic cells arise from post-germinal center B‑cells, which migrate to bone marrow (BM), adheres to the marrow stroma, and triggers subsequent bone resorption. Despite improvements in treatment, the disease remains incurable. Different molecular studies have reported genetic alterations in cytokines, adhesion molecules, oncogenes, and tumor suppressor genes (TSG) in MM. Epigenetic control of gene transcription is frequently associated with the carcinogenesis process and down-regulation of TSG by aberrant methylation contributes to the pathogenesis of various human malignancies. However, little is known about the aberrant methylation of TSG in MM. Objectives: To determine the methylation status of a 9 gene panel (RARb, p16, E-cad, DAPK1, GSTP1, MGMT, p14, MINT25 and MINT31) in MM samples and to correlate the molecular data with the patient clinical features. Methods: DNA was isolated using the TRIzol reagent (Invitrogen), as recommended by the manufacturer, from 50 BM aspirates from MM patients and from 7 controls (BM from individuals without cancer). The methylation patterns of the selected genes and CpG islands were determined by methylation-specific polymerase chain reaction analysis (MSP). Results: A pilot study with 17 MM samples showed a frequency of aberrant methylation of 71% for E‑cad, 52 % for RARb, 19% for p16, 12% for DAPK1, 12% for MGMT, and 0% for GSTP1, p14, MINT25 and MINT31. Conclusion: Our partial results suggest that RARb and E-cad are the most frequently methylated genes in MM and should have a participation in the physiopathogenesis of the MM disease.
(Supported by FAPESP).
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