Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Response to Olaparib in a PALB2 Germline Mutated Prostate Cancer and Genetic Events Associated with Resistance

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Extremely hypomorphic and severe deep intronic variants in the ABCA4 locus result in varying Stargardt disease phenotypes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The landscape of genomic alterations across childhood cancers

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. SvABA: genome-wide detection of structural variants and indels by local assembly

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Mitochondrial mutations drive prostate cancer aggression

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Peter Horak
  • Joachim Weischenfeldt
  • Gunhild von Amsberg
  • Burkhard Beyer
  • Andreas Schutte
  • Sebastian Uhrig
  • Laura Gieldon
  • Barbara Klink
  • Lars Feuerbach
  • Daniel Hubschmann
  • Simon Kreutzfeldt
  • Christoph Heining
  • Sebastian Maier
  • Barbara Hutter
  • Roland Penzel
  • Matthias Schlesner
  • Roland Eils
  • Guido Sauter
  • Albrecht Stenzinger
  • Benedikt Brors
  • Evelin Schröck
  • Hanno Glimm
  • Stefan Fröhling
  • Thorsten Schlomm
View graph of relations

Prostate cancers harboring DNA repair gene alterations might be particularly sensitive to PARP inhibitor treatment. We report a case of an advanced prostate cancer patient profiled within the NCT-MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program using next-generation sequencing. Comprehensive genomic and transcriptomic analysis identified a pathogenic germline PALB2 variant as well as a mutational signature associated with disturbed homologous recombination together with genomic structural rearrangements. A molecular tumor board concluded a potential benefit of targeted therapy and recommended PARP inhibition and platinum-based chemotherapy. Single-agent treatment with the PARP inhibitor olaparib as well as consequent combination with a platinum-based chemotherapy resulted in disease stabilization and substantial improvement of clinical symptoms. Upon progression, we performed whole-exome and RNA sequencing of a liver metastasis, which demonstrated upregulation of several genes characteristic for the neuroendocrine prostate cancer phenotype as well as a novel translocation resulting in an in-frame, loss of function fusion of RB1. We suggest that multidimensional genomic characterization of prostate cancer patients undergoing PARP inhibitor therapy will be necessary to capture and understand predictive biomarkers of PARP inhibitor sensitivity and resistance.

Original languageEnglish
JournalCold Spring Harbor Molecular Case Studies
ISSN2373-2873
DOIs
Publication statusE-pub ahead of print - 4 Mar 2019

ID: 56851868