Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches

Alessandro Mangogna; Giada Munari; Francesco Pepe; Edoardo Maffii; Pierluigi Giampaolino; Giuseppe Ricci; Matteo Fassan; Umberto Malapelle; Stefania Biffi

doi:10.3390/jpm13020284

Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches

J Pers Med. 2023 Feb 2;13(2):284. doi: 10.3390/jpm13020284.

Authors

Affiliations

¹ Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, Italy.
² Veneto Institute of Oncology, IOV-IRCCS, 35128 Padua, Italy.
³ Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
⁴ Department of Medicine (DIMED), University of Padua, 35128 Padua, Italy.
⁵ Department of Medical, Surgical and Health Science, University of Trieste, 34149 Trieste, Italy.

Abstract

The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD is a complex genomic signature, and different methods of analysis have been developed to introduce HRD testing in the clinical setting. This review describes the technical aspects and challenges related to HRD testing in ovarian cancer and outlines the potential pitfalls and challenges that can be encountered in HRD diagnostics.

Keywords: assay; homologous recombination deficiency (HRD); homologous recombination repair (HRR); next-generation sequencing (NGS); ovarian cancer; poly (ADP-ribose) polymerase inhibitor (PARPi); test.

Publication types

Review

Grants and funding

Matteo Fassan is supported by a grant from the Italian Health Ministry/Vesneto region research program NET-2016–02363853 and AIRC 5 per mille 2019 (ID. 22759 program). This work was supported by the Italian Ministry of Health, through the contribution given to the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.