Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound

Autor: Kim N. Chi, Alan Barnicle, Caroline Sibilla, Zhongwu Lai, Claire Corcoran, J. Carl Barrett, Carrie A. Adelman, Ping Qiu, Ashley Easter, Simon Dearden, Geoffrey R. Oxnard, Neeraj Agarwal, Arun Azad, Johann de Bono, Joaquin Mateo, David Olmos, Antoine Thiery-Vuillemin, Elizabeth A. Harrington
Přispěvatelé: Institut Català de la Salut, [Chi KN] BC Cancer Agency, Vancouver, Canada. [Barnicle A] Translational Medicine, AstraZeneca, Cambridge, United Kingdom. [Sibilla C, Corcoran C] Precision Medicine and Biosamples, AstraZeneca, Cambridge, United Kingdom. [Lai Z, Barrett JC] Translational Medicine, AstraZeneca, Waltham, Massachusetts. [Mateo J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2022
Předmět:
Male
BRCA2 Protein
Cancer Research
Pròstata - Càncer
Nucleic Acids
Nucleotides
and Nucleosides::Nucleic Acids::Cell-Free Nucleic Acids::Circulating Tumor DNA [CHEMICALS AND DRUGS]
BRCA1 Protein
acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS]
Antineoplastic Agents
Ataxia Telangiectasia Mutated Proteins
Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms
Male::Prostatic Neoplasms::Prostatic Neoplasms
Castration-Resistant [DISEASES]
Circulating Tumor DNA
Medicaments antineoplàstics
nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ácidos nucleicos libres de células::ADN tumoral circulante [COMPUESTOS QUÍMICOS Y DROGAS]
Prostatic Neoplasms
Castration-Resistant
Oncology
neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES]
Mutation
Biomarkers
Tumor
Humans
Cèl·lules canceroses
Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS]
Retrospective Studies
Zdroj: Scientia
ISSN: 1557-3265
1078-0432
Popis: Purpose: Not all patients with metastatic castration-resistant prostate cancer (mCRPC) have sufficient tumor tissue available for multigene molecular testing. Furthermore, samples may fail because of difficulties within the testing procedure. Optimization of screening techniques may reduce failure rates; however, a need remains for additional testing methods to detect cancers with alterations in homologous recombination repair genes. We evaluated the utility of plasma-derived circulating tumor DNA (ctDNA) in identifying deleterious BRCA1, BRCA2 (BRCA), and ATM alterations in screened patients with mCRPC from the phase III PROfound study. Patients and Methods: Tumor tissue samples were sequenced prospectively at Foundation Medicine, Inc. (FMI) using an investigational next-generation sequencing (NGS) assay based on FoundationOne®CDx to inform trial eligibility. Matched ctDNA samples were retrospectively sequenced at FMI, using an investigational assay based on FoundationOne®Liquid CDx. Results: 81% (503/619) of ctDNA samples yielded an NGS result, of which 491 had a tumor tissue result. BRCA and ATM status in tissue compared with ctDNA showed 81% positive percentage agreement and 92% negative percentage agreement, using tissue as reference. At variant-subtype level, using tissue as reference, concordance was high for nonsense (93%), splice (87%), and frameshift (86%) alterations but lower for large rearrangements (63%) and homozygous deletions (27%), with low ctDNA fraction being a limiting factor. Conclusions: We demonstrate that ctDNA can greatly complement tissue testing in identifying patients with mCRPC and BRCA or ATM alterations who are potentially suitable for receiving targeted PARP inhibitor treatments, particularly patients with no or insufficient tissue for genomic analyses.
Databáze: OpenAIRE
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