Abnormalities of the inactive X chromosome are a common feature of BRCA1 mutant and sporadic basal-like breast cancer.
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.
Ganesan
S
S
Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Richardson
A L
AL
Wang
Z C
ZC
Iglehart
J D
JD
Miron
A
A
Feunteun
J
J
Silver
D
D
Livingston
D M
DM
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006570:Heterochromatin / Q000235:genetics; D006801:Humans; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000473:pathology; D049951:X Chromosome Inactivation
D006570:Heterochromatin