BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer

Ann Oncol. 2016 Aug;27(8):1449-55. doi: 10.1093/annonc/mdw142. Epub 2016 Mar 31.

Abstract

The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice.

Keywords: BRCA; methylation; ovarian cancer; somatic mutation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • DNA Methylation / drug effects
  • Female
  • Germ-Line Mutation / genetics
  • Homologous Recombination / drug effects
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors