Abnormalities of the inactive X chromosome are a common feature of brca1 mutant and sporadic basal-like breast cancer

Abstract

As a clinical entity, breast cancer appears to be a series of subforms, each with a relatively specific molecular phenotype. Among the characteristics that differentiate these subforms are sex hormone receptor expression, HER2 expression, p53 mutation, high-grade histopathology, and particular gene expression array patterns. Sporadic basal-like breast cancer is one such form. It is a relatively common, high-grade, hormone receptor and HER2-expression- negative, p53 mutation-bearing tumor and is particularly lethal. Although wild type for BRCA1, it is a sporadic phenocopy of most cases of BRCA1-/- breast cancer. Not only do the cells of the two tumors resemble one another with respect to the above-noted characteristics, they also share a defect in the maintenance of an intact, inactive X chromosome (Xi). Other high-grade and most low-grade tumors are rarely defective at Xi. This evidence suggests that an Xi defect contributes to the evolution of both sporadic and BRCA1-/- basal-like breast tumors. © 2005 Cold Spring Harbor Laboratory Press.