RESUMO
Mutations in the BRCA1 gene, discovered in 1994, are associated with an 80-90% lifetime risk of breast cancer. We have analysed 60 families with a history of breast and/or ovarian cancer for germline mutations in BRCA1. Twenty-two different mutations were detected in 32 families (53%), of which 14 are previously unreported. We observed a significant correlation between the location of the mutation in the gene and the ratio of breast to ovarian cancer incidence within each family. Our data suggest a transition in risk such that mutations in the 3' third of the gene are associated with a lower proportion of ovarian cancer. Haplotype analysis supports previous data which suggest some BRCA1 mutation carriers have common ancestors; however, we have found at least two examples where recurrent mutations appear to have arisen independently.
Assuntos
Neoplasias da Mama/genética , Mutação em Linhagem Germinativa , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Proteína BRCA1 , Neoplasias da Mama Masculina/genética , Feminino , Marcadores Genéticos , Testes Genéticos , Genótipo , Haplótipos , Humanos , Masculino , Fenótipo , Fatores de RiscoRESUMO
This essay uses Freud to interpret the symbolism and theology of Mary in modern Catholicism. In her role as the mother of believers, Mary functions to place the Christian in the position of a child who receives illusory gratification from the mother. In her role as model for Christians to emulate, Mary functions to place the Christian in the position of receptivity and dependence which Freud associated with femininity. Reinterpreting Freud from a feminist perspective, I suggest that the kind of femininity Mary represents serves to perpetuate patriachal social structures and to inhibit full psychological maturity.
RESUMO
We screened 81 ovarian tumours (30 BRCA1 associated, 18 BRCA2 associated, and 33 sporadic) for somatic TP53 mutations using both DNA analysis and immunostaining. TP53 mutations were significantly more frequent in tumours with mutations in BRCA1 (70% by immunostaining and 60% by DNA analysis) and BRCA2 (67% and 50%) compared to sporadic controls (39% and 30%) (P = 0.009). A higher proportion of tumours with BRCA1 and BRCA2 mutations were poorly differentiated, and TP53 mutant tumours in all categories were also more likely to be poorly differentiated. The poor differentiation of tumours with BRCA1 and BRCA2 mutations may be directly related to the role of these genes in DNA repair, and the need to overcome cell cycle checkpoints, often through loss of TP53. These results are consistent with the model of BRCA-induced tumorigenesis in which loss of checkpoint control is necessary for tumour development.