BRCA1-P53 RELATIONSHIP IN HEREDITARY BREAST-CANCER

BRCA1, a major gene predisposing to breast and ovarian cancers, encode s a ring finger-containing protein. Its function is still unknown. Rec ently, the existence of a new structural domain called BRCT was postul ated. This domain has some similarity with the 53BP1 human protein inv olved in p53 binding process. To test for a possible relationship betw een BRCA1 and p53, we compared p53 expression by immunohistochemical a nalysis in 29 BRCA1-associated breast cancers from 19 families, and in 200 consecutive sporadic breast cancers. We observed a prevalence of tumors with p53 positive staining in the BRCA1 population (p=0.003). I n addition, p53 expression was affected by the site of the germ line m utation in the BRCA1 gene. p53 staining was found more consistently in tumors associated with mutations that lead to a truncation of BRCA1 i n the ring finger region (p=0.0048). These results favor the hypothesi s of a cooperation between BRCA1 and p53. Further experiments are need ed to explore the full bilogical relevance of this phenomenon.