Age-related activity of Poly (ADP-Ribose) Polymerase (PARP) in men with localized prostate cancer

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2021
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Deniz, Miriam
Zengerling, Friedemann
Gundelach, Theresa
Janni, Wolfgang
Bolenz, Christian
Kostezka, Sarah
Marienfeld, Ralf
Rall-Scharpf, Melanie
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Mechanisms of Ageing and Development. Elsevier. 2021, 196, 111494. ISSN 0047-6374. eISSN 1872-6216. Available under: doi: 10.1016/j.mad.2021.111494
Zusammenfassung

Mutations in DNA repair genes have been connected with familial prostate cancer and sensitivity to targeted drugs like PARP-inhibitors. Clinical use of this information is limited by the small fraction of prostate cancer risk gene carriers, variants of unknown pathogenicity and the focus on monogenic disease mechanisms. Functional assays capturing mono- and polygenic defects were shown to detect breast and ovarian cancer risk in blood-derived cells. Here, we comparatively analyzed lymphocytes from prostate cancer patients and controls applying a sensitive DNA double-strand break (DSB) repair assay and a flow cytometrybased assay measuring the activity of Poly(ADP-Ribose)-Polymerase, a target in treatment of metastatic prostate cancer. Contrary to breast and ovarian cancer patients, error-prone DNA double-strand break repair was not activated in prostate cancer patients. Yet, the activity of PARP discriminated between prostate cancer cases and controls. PARylation also correlated with the age of male probands, suggesting male-specific links between mutation-based and aging-associated DNA damage accumulation and PARP. Our work identifies prostate cancer-specific DNA repair phenotypes characterized by increased PARP activities and carboplatin-sensitivities, detected by functional testing of lymphocytes. This provides new insights for further investigation of PARP and carboplatin sensitivity as biomarkers in peripheral cells of men and prostate cancer patients.

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570 Biowissenschaften, Biologie
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Prostate cancer, Poly (ADP-Ribose)-Polymerase activity, DSB-Repair, Functional analysis
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ISO 690DENIZ, Miriam, Friedemann ZENGERLING, Theresa GUNDELACH, Maria MORENO-VILLANUEVA, Alexander BÜRKLE, Wolfgang JANNI, Christian BOLENZ, Sarah KOSTEZKA, Ralf MARIENFELD, Melanie RALL-SCHARPF, 2021. Age-related activity of Poly (ADP-Ribose) Polymerase (PARP) in men with localized prostate cancer. In: Mechanisms of Ageing and Development. Elsevier. 2021, 196, 111494. ISSN 0047-6374. eISSN 1872-6216. Available under: doi: 10.1016/j.mad.2021.111494
BibTex
@article{Deniz2021-04-19Agere-53631,
  year={2021},
  doi={10.1016/j.mad.2021.111494},
  title={Age-related activity of Poly (ADP-Ribose) Polymerase (PARP) in men with localized prostate cancer},
  volume={196},
  issn={0047-6374},
  journal={Mechanisms of Ageing and Development},
  author={Deniz, Miriam and Zengerling, Friedemann and Gundelach, Theresa and Moreno-Villanueva, Maria and Bürkle, Alexander and Janni, Wolfgang and Bolenz, Christian and Kostezka, Sarah and Marienfeld, Ralf and Rall-Scharpf, Melanie},
  note={Article Number: 111494}
}
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