A role of X chromosome inactivation process in the development of
breast cancer have been suggested. In particular, the relationship between the
breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of
breast carcinomas and in a panel of
breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of
heterochromatin in relation to BRCA1 status in
breast cancer cells. We provide evidence that in
breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in
cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global
heterochromatin defects observed in
breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast
carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related
cancers. Moreover, the significant higher levels of XIST-
RNA detected in BRCA1-associated respect to sporadic basal-like
cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of
tumors.