BRCA1 mutations and luminal-basal transformation

Abstract

The multifunctional roles of BRCA1 include its ability to regulate transcriptional processes that control differentiation at multiple levels, as well as functioning as a tumor suppressor. Data herein demonstrate that germline mutations in Brca1 impair luminal cell lineage and mammary development, with its deficiency converting ER-positive luminal tumors into basal-like cancers. Heterozygous mutations in Brca1 lead to downregulation of a number of luminal differentiation genes, explaining how it suppresses basal-like tumors, also highlighting its importance outside of its known highly publicized role in DNA repair.