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Methylation of tumor suppressor genes in venezuelan patients with acute lymphoid leukemia.

Abstract:

Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in children. A specific methylation profile of CpG islands in the promoter regions of tumor suppressor genes has been demonstrated, which plays a critical role in transcriptional silencing and may offer new treatment options. In order to determine this profile, the methylation status of CpG islands was analyzed in the promoter region of four tumor suppressor genes associated with different stages of carcinogenesis: two associated with the regulation of cell cycle and apoptosis: p15 and p73; and two involved in migration and tumor metastasis: E-cadherin and RARβ2. Thirty peripheral blood samples were analyzed by modification of DNA with sodium bisulfite and chain reaction polymerase specific for methylation. In all patients, the methylation of at least one gene was observed (100%) and additionally, there were specific methylation frequencies of 76.67% for the p73 gene (23 patients); 56.67% for p15 (seven patients); 16.67% for E-cadherin (five patients) and 20.0% for the RARβ2 (six patients). The frequency of methylation observed in p15 and p73 genes suggests the important role of these genes in the pathogenesis of ALL and its usefulness in risk assessment and the selection of the most appropriate treatment.