Here we used a combination of genomic profiling of human normal and DCIS breast tissues and functional assays in the MCF10DCIS experimental model of DCIS32 to investigate determinants of normal myoepithelial cell differentiation and perturbations of these in BRCA1 and BRCA2 germline mutation carriers and in DCIS. The gene discussed is BRCA2; the disease is ductal breast carcinoma in situ.