RESUMEN
A proportion of extraskeletal myxoid chondrosarcomas (EMC) have been shown to have a characteristic translocation t(9;22)(q22;q12) involving the EWS gene at 22q12 and the CHN orphan nuclear receptor gene at 9q22. This translocation appears to be largely specific for EMC, but has not been detected in all such tumours. We report here a case of EMC with a t(9;17)(q22;q11.2) as the sole chromosome abnormality. We have determined that the translocation results in the fusion of the entire coding region of CHN to the N-terminal transactivation domain of RBP56/hTAFII68. This is the first report of a translocation involving RBP56/hTAFII 68, a protein with sequence homology to both EWS and TLS/FUS. The involvement of RBP56/hTAFII68 may explain some unusual features of the tumour.
Asunto(s)
Fusión Artificial Génica , Condrosarcoma/genética , Proteínas de Unión al ADN/genética , Proteínas del Tejido Nervioso , Proteínas Nucleares/genética , Factores Asociados con la Proteína de Unión a TATA , Factores de Transcripción/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 9 , Humanos , Datos de Secuencia Molecular , Receptores de Esteroides , Receptores de Hormona Tiroidea , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación GenéticaRESUMEN
Germline TP53 splicing mutations have been described infrequently (>2%) in the literature, however in a series of 40 patients and families identified by our group in which there are germline TP53 mutations, seven affect splicing (18%). The low figure reported in the literature might reflect the method of mutation detection, which in many studies does not include all splice junctions. These data indicate that a significant proportion of TP53 germline mutations are currently unrecognized. We have carried out detailed studies of the effects of the different mutations on splicing, and see distinct variations in the effects of the same mutation in different patients. Furthermore we have identified the usage of a non-consensus splice donor site in four families with an intron 4 splice donor mutation.
Asunto(s)
Empalme Alternativo/fisiología , Genes p53/genética , Mutación de Línea Germinal/fisiología , Empalme Alternativo/genética , Línea Celular , Fibroblastos/fisiología , Mutación de Línea Germinal/genética , Humanos , Inmunohistoquímica , Intrones , Síndrome de Li-Fraumeni/genética , Pérdida de Heterocigocidad , Linfocitos/fisiología , Neoplasias/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/fisiologíaRESUMEN
A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported. Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.