Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer. 2021

David Gonzalez, and Joaquin Mateo, and Albrecht Stenzinger, and Federico Rojo, and Michelle Shiller, and Alexander W Wyatt, and Frédérique Penault-Llorca, and Leonard G Gomella, and Ros Eeles, and Anders Bjartell
Patrick G Johnston Centre for Cancer Research, Queen's University, Belfast, UK.

Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of patients with mCRPC to identify those who can benefit from targeted therapies. Best practice guidelines in overall biospecimen collection and processing for molecular analysis are widely available for several tumour types. However, there is no standard protocol for molecular diagnostic testing in prostate cancer. Here, we provide a series of recommendations on specimen handling, sample pre-analytics, laboratory workflow, and testing pathways to maximise the success rates for clinical genomic analysis in prostate cancer. Early involvement of a multidisciplinary team of pathologists, urologists, oncologists, radiologists, nurses, molecular scientists, and laboratory staff is key to enable optimal workflow for specimen selection and preservation at the time of diagnosis so that samples are available for molecular analysis when required. Given the improved outcome of patients with mCRPC and homologous recombination repair gene alterations who have been treated with PARP inhibitors, there is an urgent need to incorporate high-quality genomic testing in the routine clinical pathway of these patients.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297 Male Males
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010793 Phthalazines Bicyclic heterocyclic compounds containing a BENZENE ring fused to PYRIDAZINE.
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067856 Poly(ADP-ribose) Polymerase Inhibitors Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES. Inhibitors of Poly(ADP-ribose) Polymerase,PARP Inhibitor,Poly(ADP-Ribose) Polymerase Inhibitor,Poly(ADP-ribosylation) Inhibitor,Inhibitors of Poly(ADP-ribose) Polymerases,PARP Inhibitors,Poly(ADP-ribosylation) Inhibitors,Inhibitor, PARP,Inhibitors, PARP
D057089 Pathology, Molecular A subspecialty of pathology concerned with the molecular basis (e.g., mutations) of various diseases. Diagnostic Molecular Pathology,Molecular Diagnostics,Diagnostic Molecular Pathologies,Diagnostic, Molecular,Diagnostics, Molecular,Molecular Diagnostic,Molecular Pathologies,Molecular Pathologies, Diagnostic,Molecular Pathology,Molecular Pathology, Diagnostic,Pathologies, Diagnostic Molecular,Pathologies, Molecular,Pathology, Diagnostic Molecular
D059767 Recombinational DNA Repair Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids. Homologous Recombination DNA Repair,Homologous Recombination Repair of DNA,Homology-Directed dsDNA Break Repair,Homologous Recombination Double-Stranded Break DNA Repair,Homologous Recombination Repair,Homologous Recombinational Repair,Recombination Repair,Recombinational Repair of DNA,DNA Recombinational Repair,DNA Repair, Recombinational,Homologous Recombination Double Stranded Break DNA Repair,Homologous Recombinational Repairs,Homology Directed dsDNA Break Repair,Recombination Repair, Homologous,Recombinational Repair, Homologous,Repair, Homologous Recombinational,Repair, Recombination,Repair, Recombinational DNA

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