Assays for Hypermethylation of the BRCA1 Gene Promoter in Tumor Cells to Predict Sensitivity to PARP-Inhibitor Therapy

  • Ilsiya Ibragimova
  • Paul Cairns
Part of the Methods in Molecular Biology book series (MIMB, volume 780)


The breast cancer 1 and 2, early onset (BRCA1 and BRCA2) genes are important for double-strand break repair by homologous recombination. Cells with inactivating mutations of the BRCA1 or BRCA2 tumor suppressor genes show increased sensitivity to Poly-ADP ribose polymerase (PARP)-inhibitors in vitro. Sporadic breast tumors with BRCA1 promoter hypermethylation show a similar phenotype to familial BRCA1 patient tumors termed “BRCAness.” Sporadic ovarian tumors with functional inactivation of BRCA1 by hypermethylation will also have the BRCA-deficiency phenocopy. The loss of BRCA1 expression associated with promoter hypermethylation will disrupt BRCA-associated DNA repair and may sensitize tumors to BRCA-directed therapies. Thus, the determination of methylation status of BRCA1 may 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 of BRCA1 and/or other genes.

Key words

BRCA1 Hypermethylation PARP Bisulfite sequencing Pyrosequencing Quantitative MSP Methylation beadchip 



This work was supported by the Ovarian Cancer SPORE at Fox Chase Cancer Center (P50 CA083638).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ilsiya Ibragimova
    • 1
  • Paul Cairns
    • 1
  1. 1.Departments of Surgical Oncology and PathologyFox Chase Cancer CenterPhiladelphiaUSA

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