{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:33:48Z","timestamp":1790573628409,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>the homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short variant\u2013mutated (svmut), and BRCA2\u2013wild type (wt) clinically advanced prostate carcinoma (CAPC) samples, combined with an assessment of HRDsig status to gain a better understanding of these biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Comprehensive genomic profiling (CGP) was performed on 22\u00a0061 CAPC cases to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic ancestry, were derived from sequencing data. HRDsig status was calculated using genome-wide copy number features. PD-L1 expression was assessed by IHC. Comparisons were performed using Fisher\u2019s exact test with Benjamini\u2013Hochberg correction for false discovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 22\u00a0061 CAPC cases, 10.2% were HRDsig+. HRDsig+ and were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations, while SPOP, MSI-high, high TMB, and MMR signatures were more frequent in HRDsig\u2212 cases. Across BRCA2-defined subgroups, 597 (2.7%) were BRCA2-loss, 1085 (4.9%) BRCA2-svmut, and 20\u00a0379 (92.4%) BRCA2-wt. Both BRCA2-loss and BRCA2-svmut were associated with higher GA burden and enrichment for RB1 alterations. BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence. Most BRCA2 alterations were bi-allelic, with concurrent alterations in other HRR genes being rare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag100","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:42:27Z","timestamp":1774010547000},"source":"Crossref","is-referenced-by-count":1,"title":["Homologous recombination deficiency and genomic alterations in advanced prostate cancer: insights for precision therapy"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-1776","authenticated-orcid":false,"given":"Chiara","family":"Mercinelli","sequence":"first","affiliation":[{"name":"Vita-Salute San Raffaele University , Via Olgettina 60 , Milan, 20132,","place":["Italy"]},{"name":"IRCCS San Raffaele Hospital, Comprehensive Cancer Center Department of Medical Oncology, , Via Olgettina 60 , 20132, Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-6246","authenticated-orcid":false,"given":"Dean","family":"Pavlick","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc , Cambridge, MA, 02141-2115,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1076-0428","authenticated-orcid":false,"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Department of Medical Oncology, , Salt Lake City, UT, 84112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-1972","authenticated-orcid":false,"given":"Philippe E","family":"Spiess","sequence":"additional","affiliation":[{"name":"H. 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Lee Moffitt Cancer Center and Research Institute Department of Genito-Urinary Oncology, , Tampa, FL, 33612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish M","family":"Kamat","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center Department of Urology, , Houston, TX, 77030,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Grivas","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, University of Washington , Seattle, WA, 98109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8775-503X","authenticated-orcid":false,"given":"Shilpa","family":"Gupta","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Taussig Cancer Institute , Cleveland, OH, 44195,","place":["United 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Olgettina 60 , 20132, Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Piacentini","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Hospital, Comprehensive Cancer Center Department of Medical Oncology, , Via Olgettina 60 , 20132, Milan,","place":["Italy"]},{"name":"University of Verona and University Hospital Trust (AOUI) Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), , Verona, 37124,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M","family":"Jacob","sequence":"additional","affiliation":[{"name":"Upstate Medical University Department of Urology, , Syracuse, NY, 13210,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Bratslavsky","sequence":"additional","affiliation":[{"name":"Upstate Medical University Department of Urology, , Syracuse, NY, 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