RESUMO
BACKGROUND: Activation mutations of SH3BP2 gene have been demonstrated in cherubism and central giant cell lesion (CGCL). In the present study we first attempted to investigate the SH3BP2 gene in peripheral giant cell lesion (PGCL). The effect of SH3BP2 gene mutations on the transcription of the downstream genes nuclear factor of activated T cells (NFATc1) and the cytokine tumor necrosis factor-alpha (TNF-alpha) was also investigated together with the immunolocalization of NFATc1 protein in a set of cases of PGCL, CGCL and cherubism with and without SH3BP2 mutation. METHOD: Fresh samples of five PGCL, five CGCL and one cherubism cases were included in this study. One of the samples of CGCL presented a somatic heterozygous mutation c.1442A>T in exon 11. The cherubism case showed a heterozygotic substitution c.320C>T in both blood and lesion. These mutations were previously published. All coding and flanking regions of the SH3BP2 gene were sequenced in the cases of PGCL. The real-time polymerase chain reaction (RT-PCR) was performed to analyze the transcription of NFATc1 and TNF-alpha genes. The immunohistochemical analysis of the NFATc1 protein was also performed. RESULTS: No SH3BP2 gene mutation was found in PGCL. The RT-PCR showed increased expression of NFATc1 and decreased transcription of TNF-alpha in all the samples. The immunohistochemical analysis of the NFATc1 protein showed a predominant nuclear staining in the multinucleated giant cells. CONCLUSION: The development of giant cells lesions of the jaws and cherubism are possibly mediated by overexpression of NFAT in the nucleus of the multinucleated cells.
Assuntos
Querubismo/genética , Granuloma de Células Gigantes/genética , Doenças Maxilomandibulares/genética , Mutação/genética , Fatores de Transcrição NFATC/genética , Fator de Necrose Tumoral alfa/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina , Núcleo Celular/ultraestrutura , Querubismo/sangue , Querubismo/patologia , Citosina , Éxons/genética , Regulação da Expressão Gênica/genética , Células Gigantes/patologia , Glutamina/genética , Granuloma de Células Gigantes/patologia , Heterozigoto , Humanos , Doenças Maxilomandibulares/patologia , Leucina/genética , Metionina/genética , Fatores de Transcrição NFATC/análise , Polimorfismo Genético/genética , Treonina/genética , Timina , Transcrição Gênica/genética , Fator de Necrose Tumoral alfa/análise , Domínios de Homologia de src/genéticaRESUMO
Cherubism is an autosomal dominant inherited syndrome characterized by excessive bone degradation of upper and lower jaw and its replacement with large amounts of fibrous tissue, which causes a characteristic facial swelling. A correlation with a mutation in the gene SH3BP2 has been previously demonstrated, but a model for its pathogenesis is not yet available. Here we describe a novel mutation in an aggressive case of cherubism located in the pleckstrin homology domain (PH) of the SH3BP2.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Querubismo/genética , Mutação , Sequência de Bases , Criança , Análise Mutacional de DNA , Humanos , Masculino , Dados de Sequência Molecular , Domínios de Homologia de srcRESUMO
BACKGROUND: Ameloblastin (AMBN) gene expresses an important protein that acts as a cell adhesion molecule. This protein plays an important role in maintaining the ameloblast secretory stage of differentiation by binding to them and inhibiting their proliferation. Due to the relationship of this protein in the differentiation and proliferation of odontogenic cells, here, we investigated this gene in different types of odontogenic tumors. MATERIALS AND METHODS: Sequencing of the all encoding region of AMBN gene was carried out in four frozen cases of odontogenic tumors: one case of calcifying epithelial odontogenic tumor (CEOT), two calcifying odontogenic cysts (COC) and one ameloblastic fibroma (AF). RESULTS: DNA sequencing was modified in an important domain of the AMBN only in the CEOT. CONCLUSION: The present study suggests that AMBN gene alterations may be relevant to the pathogenesis of CEOT.
Assuntos
Ameloblastos/patologia , Calcinose/patologia , Proteínas do Esmalte Dentário/genética , Células Epiteliais/patologia , Fibroma/patologia , Mutação/genética , Tumores Odontogênicos/genética , Análise Mutacional de DNA , Humanos , Tumores Odontogênicos/patologiaRESUMO
The glycogen storage disease (GSD) is a group of inherited disorders that involve deficiencies in the enzymes that metabolize glycogen. The purpose of the present paper is to report a rare case of GSD type 1b that presented both peripheral and central giant cell granuloma, and to discuss the possible explanation for this unusual finding. The use of corticosteroids in the management of central giant cell granuloma is also demonstrated.