RESUMO
BHD, TP53, and HNF1beta on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1beta mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.
Assuntos
Carcinoma de Células Renais/genética , Genes p53 , Fator 1-beta Nuclear de Hepatócito/genética , Neoplasias Renais/genética , Mutação , Proteínas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Supressoras de Tumor/genética , Humanos , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Genes do Retinoblastoma , Mutação Puntual , Sítios de Splice de RNA , Proteína do Retinoblastoma/genética , Retinoblastoma/genética , Pré-Escolar , Éxons , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Lactente , Masculino , Linhagem , Penetrância , Nucleotídeos de Pirimidina/genética , RNA Neoplásico/análise , Retinoblastoma/metabolismoRESUMO
Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.
