Whole-genome sequencing identifies homozygous BRCA2 deletion guiding treatment in dedifferentiated prostate cancer

Cold Spring Harb Mol Case Stud. 2017 May;3(3):a001362. doi: 10.1101/mcs.a001362.

Abstract

Whole-genome sequencing (WGS) has transformed the understanding of the genetic drivers of cancer and is increasingly being used in cancer medicine to identify personalized therapies. Here we describe a case in which the application of WGS identified a tumoral BRCA2 deletion in a patient with aggressive dedifferentiated prostate cancer that was repeat-biopsied after disease progression. This would not have been detected by standard BRCA testing, and it led to additional treatment with a maintenance poly ADP ribose polymerase (PARP) inhibitor following platinum-based chemotherapy. This case demonstrates that repeat biopsy upon disease progression and application of WGS to tumor samples has meaningful clinical utility and the potential to transform outcomes in patients with cancer.

Keywords: malignant genitourinary tract tumor; prostate cancer.

Publication types

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

MeSH terms

  • BRCA2 Protein / genetics*
  • BRCA2 Protein / metabolism
  • Biopsy / methods
  • Germ-Line Mutation
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / therapeutic use
  • Precision Medicine
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / therapy*
  • Sequence Deletion
  • Whole Genome Sequencing / methods

Substances

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