Thebreast cancer 1and2,early onset(BRCA1andBRCA2) genes are important for double-strand break repair by homologous recombination. Cells with inactivating mutations of theBRCA1orBRCA2tumor suppressor genes show increased sensitivity to Poly-ADP ribose polymerase (PARP)-inhibitors in vitro. Sporadic breast tumors withBRCA1promoter hypermethylation show a similar phenotype to familialBRCA1patient tumors termed “BRCAness.” Sporadic ovarian tumors with functional inactivation ofBRCA1by hypermethylation will also have the BRCA-deficiency phenocopy. The loss ofBRCA1expression associated with promoter hypermethylation will disrupt BRCA-associated DNA repair and may sensitize tumors to BRCA-directed therapies. Thus, the determination of methylation status ofBRCA1may be an important predictive classifier of response to PARP-inhibitor therapy. The methylation, and thereby functional, status of other genes implicated in the wider BRCA/homologous recombination (HR) pathway may also be relevant to the prediction of response to PARP-inhibitor therapy. Here, we describe the four optimal technologies for assaying the promoter methylation status ofBRCA1and/or other genes.
