Heterozygote BRCA1 status and skewed chromosome X inactivation

A high frequency of skewed X-chromosome inactivation has been reported in peripheral blood lymphocytes from early onset breast cancer or invasive ovarian cancer patients. Recent findings have shown that breast and ovarian carcinoma cells from BRCA1 mutation carrier women lack the hallmarks of inactive X chromatin structure. These observations suggested that loss of functional BRCA1 in female cells may perturb the process of X inactivation and have lead us to the hypothesis that analysis of skewing could be used as a predictive test for BRCA1 germline mutation in lymphocytes from breast cancer patients. In the present study, we have compared the X inactivation pattern in lymphoblastoid cell lines from 38 females carrying heterozygous BRCA1 mutation to 41 controls. X inactivation analysis was assessed on the polymorphic CAG repeat within the human androgen receptor gene. Our observations rule out an effect of a monoallelic BRCA1 germline mutation on the choice of inactivated chromosome X and therefore the possibility of using analysis of Xi skewing as a predictive test for BRCA1 germline mutation carrier status.