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

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Poly(ADP-ribose) Polymerase

Part of the book series: Methods in Molecular Biology ((MIMB,volume 780))

Abstract

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.

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Acknowledgment

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

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Authors and Affiliations

  1. Departments of Surgical Oncology and Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA

    Ilsiya Ibragimova & Paul Cairns

Authors
  1. Ilsiya Ibragimova
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  2. Paul Cairns
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Editors and Affiliations

  1. Keystone Program in Epigenetics &, Progenitor Cells, Fox Chase Cancer Center, Cottman Avenue 333, Philadelphia, 19111, Pennsylvania, USA

    Alexei V. Tulin

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Ibragimova, I., Cairns, P. (2011). Assays for Hypermethylation of the BRCA1 Gene Promoter in Tumor Cells to Predict Sensitivity to PARP-Inhibitor Therapy. In: Tulin, A. (eds) Poly(ADP-ribose) Polymerase. Methods in Molecular Biology, vol 780. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-270-0_17

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  • DOI: https://doi.org/10.1007/978-1-61779-270-0_17

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-269-4

  • Online ISBN: 978-1-61779-270-0

  • eBook Packages: Springer Protocols

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