Methylation analysis of the CDKN2B and DBC1 tumour suppressor genes in leukaemia patients in Colombia
Keywords:
DNA methylation, Leukaemia, ALL, AML, CML, Epigenetics, Tumour suppressor genesAbstract
Objective: To perform a methylation analysis in the CDKN2B and DBC1 gene promoters in samples from Colombian patients with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and chronic myeloid leukaemia (CML), and to correlate the methylation profile with cytogenetic findings.
Material and methods: The study included a total of 56 bone marrow samples, 24 from patients with ALL, 16 from AML patients, and 16 from CML patients. DNA was extracted from these samples and converted with sodium bisulphite. Methylation analysis was performed using methylation specific PCR (MS-PCR). The samples that were positive for MS-PCR were sequenced to confirm the results.
Results: A total methylation frequency of 87.5% was found. CDKN2B gene promoter hypermethylation was found in 75% of ALL and CML samples, and 62% in AML; while DBC1 gene promoter hypermethylation was found in 96% of the samples of ALL, 94% of AML, and in 68.8% of CML.
The most frequently methylated gene in all samples was DBC1. ALL was the type of leukaemia that had the highest percentages of methylation. Almost two-thirds (62.5%) of the samples had both methylated genes. Samples with normal karyotype had a high frequency of methylation in CDKN2B and DBC1 genes.
Conclusions: This study showed, for the first time in Colombian patients with leukaemia, that methylation of DBC1 and CDKN2B genes is a common event. Our findings indicate that methylation of tumour suppressor genes is an alternate genetic pathway related to the development
of haematological malignancies.
Author Biographies
Laura María Medina Gómez, Universidad de Antioquia
Unidad de Genética Médica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
Gonzalo Vásquez Palacio, Universidad de Antioquia
Unidad de Genética Médica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
Carlos Mario Muñetón Peña, Universidad de Antioquia
Unidad de Genética Médica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
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