RESUMEN
OBJECTIVE: To investigate HRPT2 in jaw ossifying fibroma (OF), fibrous dysplasia (FD), and osteosarcoma (OS). STUDY DESIGN: We combined microsatellite loss of heterozygosity (LOH), HRPT2 sequence alterations at the mRNA level by reverse-transcription polymerase chain reaction (PCR), cDNA sequencing, and quantitative PCR (qPCR) and immunohistochemistry (IHC) in a total of 19 OF, 15 FD, and 9 OS. Because HRPT2 (parafibromin) interacts with cyclin D1, we investigated cyclin D1 expression with the use of qPCR and IHC. RESULTS: LOH was detected in 3/5 FD, 6/9 OF, and 2/2 OS heterozygous samples. LOH was not associated with decreased mRNA levels or HRPT2 protein expression except for 1 OF which harbored an inactivating mutation. However, this tumor did not display altered transcription or protein levels of HRPT2 nor cyclin compared with the other OF. CONCLUSIONS: The contribution of HRPT2 inactivation to the pathogenesis of OF, FD, and OS is marginal at best and may be limited to progression rather than tumor initiation.
Asunto(s)
Fibroma Osificante/genética , Displasia Fibrosa Ósea/genética , Hiperparatiroidismo/genética , Enfermedades Maxilomandibulares/genética , Neoplasias Maxilomandibulares/genética , Osteosarcoma/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Anciano , Mapeo Cromosómico , Cromosomas Humanos Par 1/genética , Ciclina D1/genética , Progresión de la Enfermedad , Exones/genética , Femenino , Silenciador del Gen , Humanos , Pérdida de Heterocigocidad/genética , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Mutación/genética , ARN Mensajero/genética , Eliminación de Secuencia/genética , Transcripción Genética/genética , Adulto JovenRESUMEN
WWOX is a tumour suppressor gene altered in various human neoplasms. Deletion of WWOX is associated with bone metabolic defects and development of osteosarcoma in mice. We hypothesized that alterations of this gene are associated with the development of benign and malignant mesenchymal bone related lesions of the jaws. We investigated WWOX mRNA by nested reverse transcription-PCR and direct sequencing and quantitative real-time PCR in two osteosarcoma, two fibrosarcoma, eight ossifying fibroma and two fibrous dysplasia fresh samples. Malignancy was associated with a decreased WWOX mRNA expression. Aberrant transcription pattern was found in five samples; however, the relative quantification (RQ) of the WWOX mRNA in such lesions was not different from those carrying only the wild-type. We provide new evidence of WWOX alterations in osteosarcomas and demonstrate for the first time alterations of this gene in fibrosarcomas as well as in ossifying fibromas of the jaws.