RESUMEN
Germline mutation of the BRCA2 gene carries a high risk of developing breast cancer. To study the function of this gene, we generated a mutation in Brca2 in mice. Unlike other mutations in the Brca2 gene, which are lethal early in embryogenesis when homozygous, some of our homozygous mutant mice survive to adulthood. These animals have a wide range of defects, including small size, improper differentiation of tissues, absence of germ cells and the development of lethal thymic lymphomas. Fibroblasts cultured from BrcaZ-/-embryos have a defect in proliferation that may be mediated by over-expression of p53 and p21Waf1/CIP1. We show that Brca2 is required for efficient DNA repair, and our results suggest that loss of the p53 checkpoint may be essential for tumour progression triggered by mutations in BRCA2.
Asunto(s)
Neoplasias de la Mama/genética , Reparación del ADN/genética , Eliminación de Gen , Mutación de Línea Germinal , Proteínas de Neoplasias/genética , Factores de Transcripción/genética , Animales , Proteína BRCA2 , Neoplasias de la Mama/embriología , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Células Cultivadas , Cruzamientos Genéticos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/genética , Desarrollo Embrionario y Fetal/genética , Femenino , Fibroblastos/metabolismo , Genes Letales , Linfoma de Células T/embriología , Linfoma de Células T/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Endogámicos DBA , Ratones Noqueados , Mutagénesis Insercional , Espermatogénesis/genética , Testículo/patología , Neoplasias del Timo/embriología , Neoplasias del Timo/genética , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Primary thymic seminoma is a rare germ cell neoplasm histologically identical to testicular seminoma. About 100 cases have been reported in the world literature. The most probable pathogenic theory is abnormal migration of germinal cells from the vitelline sac to the embryonic thymus. Management involves surgery and radiotherapy. The extreme radiosensitivity of the tumor is responsible for a 5-years survival rate of 75 per cent. Thymic seminomas are usually found in young men. We report the case of a 49 year female in whom the combination of surgery and radiotherapy followed by chemotherapy provided excellent results.