RESUMO
OBJECTIVE: The benign epithelial odontogenic tumours constitute a group of lesions derived from epithelial elements of the tooth-forming apparatus. This group includes lesions of different biological behaviour, such as ameloblastoma, calcifying cystic odontogenic tumour (CCOT) and adenomatoid odontogenic tumour (AOT). The pathogenesis of these neoplasms remains uncertain and the occurrence of methylation in cell-cycle related genes may be involved in their development. The aim of this study was to investigate the methylation status of P16, P21, P27, P53 and RB1 genes in epithelial odontogenic tumours. DESIGN: Methylation-specific polymerase chain reaction (MSP) was used to evaluate the presence of methylation in 13 samples of ameloblastoma, six samples of CCOT, three samples of AOT and 14 samples of dental follicles, included as control. RESULTS: Our results showed a distinct methylation profile in each group. In ameloblastoma, the highest methylated genes were P16 and P21, while in CCOT the P21 and RB1 genes were the most commonly methylated genes. Only the P16 and P21 genes were methylated in the AOT samples. In the dental follicle samples, P16, P27 and RB1 genes were commonly methylated. A high percentage of the odontogenic tumours analysed showed methylation of the P21 gene, in contrast to dental follicles. CONCLUSIONS: Epithelial odontogenic tumours show a distinct methylation profile in cell-cycle associated genes. In addition to this, the current findings show that epigenetic alterations are common events in epithelial odontogenic tumours.
Assuntos
Proteínas de Ciclo Celular/genética , Metilação de DNA/genética , DNA de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Tumores Odontogênicos/genética , Adenoma/genética , Adenoma/metabolismo , Ameloblastoma/genética , Ameloblastoma/metabolismo , Proteínas de Ciclo Celular/metabolismo , Saco Dentário/metabolismo , Células Epiteliais/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Cisto Odontogênico Calcificante/genética , Cisto Odontogênico Calcificante/metabolismo , Tumores Odontogênicos/metabolismo , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: Odontogenic keratocyst (OKC) is a benign neoplasm with an aggressive clinical behavior and a high recurrence rate. Although epigenetic alterations have been reported in different tumors, these events were not investigated in OKC yet. The aim of this study was to investigate the presence of methylation in P16, P21, P27, P53 and RB1 genes in OKC tumors. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to evaluate the presence of methylation in 10 samples of OKCs, 10 samples of dental follicles and six samples of normal mucosa. RESULTS: The methylation status of the P16 gene was similar among the three groups. In P21 gene, 30% of OKCs were methylated while no methylation could be detected in the other groups. High frequency of P27 methylation (90%) was observed in dental follicles, however, some OKC lesions (10%) and normal mucosa samples (33%) were also methylated. Concerning the RB1 gene, positive results were detected only in dental follicles (40%). No positive result was observed considering P53 gene. CONCLUSIONS: Our data show methylation of the promoter of P21 gene in OKCs. In addition, methylation of the P27 and RB1 genes are commonly found in dental follicles. Further studies are necessary to determine the functional relevance of these alterations.
