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oai:recercat.cat:11351/96702025-05-04T02:55:29Zcom_2072_378070com_2072_378040col_2072_378092

Genomic Biomarkers and Genome-Wide Loss-of-Heterozygosity Scores in Metastatic Prostate Cancer Following Progression on Androgen-Targeting Therapies Zurita, Amado J. Graf, Ryon Raskina, Kira Sokol, Ethan Jin, Dexter Casanova Salas, Irene Villacampa Javierre, Guillermo Vivancos, Ana Mateo, Joaquin Carles, Joan Institut Català de la Salut [Zurita AJ] The University of Texas MD Anderson Cancer Center, Houston, TX. [Graf RP, Raskina K, Sokol E, Jin D] Foundation Medicine Inc, Cambridge, MA. [Villacampa G, Casanova-Salas I, Vivancos A, Carles J, Mateo J] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Marcadors tumorals Pròstata - Càncer - Tractament Andrògens - Ús terapèutic DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Androgens Other subheadings::Other subheadings::/therapeutic use ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::hormonas, sustitutos de hormonas y antagonistas de hormonas::hormonas::andrógenos Otros calificadores::Otros calificadores::/uso terapéutico Genomic biomarkers; Prostate cancer; Targeting therapies Biomarcadores genómicos; Cáncer de próstata; Terapias dirigidas Biomarcadors genòmics; Càncer de pròstata; Teràpies dirigides PURPOSE To study the impact of standard-of-care hormonal therapies on metastatic prostate cancer (mPC) clinical genomic profiles in real-world practice, with a focus on homologous recombination-repair (HRR) genes. PATIENTS AND METHODS Targeted next-generation sequencing of 1,302 patients with mPC was pursued using the FoundationOne or FoundationOne CDx assays. Longitudinal clinical data for correlative analysis were curated via technology-enabled abstraction of electronic health records. Genomic biomarkers, including individual gene aberrations and genome-wide loss-of-heterozygosity (gLOH) scores, were compared according to biopsy location and time of sample acquisition (androgen deprivation therapy [ADT]-naïve, ADT-progression and post-ADT, and novel hormonal therapies [NHT]-progression), using chi-square and Wilcoxon rank-sum tests. Multivariable analysis used linear regression. False-discovery rate of 0.05 was applied to account for multiple comparisons. RESULTS Eight hundred forty (65%), 132 (10%), and 330 (25%) biopsies were ADT-naïve, ADT-progression, and NHT-progression, respectively. Later-stage samples were enriched for AR, MYC, TP53, PTEN, and RB1 aberrations (all adjusted P values < .05), but prevalence of HRR-related BRCA2, ATM, and CDK12 aberrations remained stable. Primary and metastatic ADT-naïve biopsies presented similar prevalence of TP53 (36% v 31%) and BRCA2 (8% v 7%) aberrations; 81% of ADT-naïve BRCA2-mutated samples presented BRCA2 biallelic loss. Higher gLOH scores were independently associated with HRR genes (BRCA2, PALB2, and FANCA), TP53, and RB1 aberrations, and with prior exposure to hormonal therapies in multivariable analysis. CONCLUSION Prevalence of HRR-gene aberrations remains stable along mPC progression, supporting the use of diagnostic biopsies to guide poly (ADP-ribose) polymerase inhibitor treatment in metastatic castration-resistant prostate cancer. gLOH scores increase with emerging resistance to hormonal therapies, independently of individual HRR gene mutations. 2023-06-06T08:40:18Z 2023-06-06T08:40:18Z 2022-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Zurita AJ, Graf RP, Villacampa G, Raskina K, Sokol E, Jin D, et al. Genomic Biomarkers and Genome-Wide Loss-of-Heterozygosity Scores in Metastatic Prostate Cancer Following Progression on Androgen-Targeting Therapies. JCO Precis Oncol. 2022 Jul;6:e2200195. 2473-4284 https://hdl.handle.net/11351/9670 10.1200/PO.22.00195 35820087 000975488400076 eng JCO Precision Oncology;6 https://doi.org/10.1200/PO.22.00195 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf American Society of Clinical Oncology Scientia