{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T14:27:38Z","timestamp":1765376858053,"version":"3.46.0"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-15-00262"],"award-info":[{"award-number":["23-15-00262"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Homologous recombination deficiency (HRD) resulting from inactivation of BRCA1\/2 genes promotes chromosomal instability and renders tumor cells susceptible to platinum derivatives and PARP inhibitors (PARPi). The contribution of alterations in other homologous recombination repair (HRR) genes to HRD remains understudied. This investigation aimed to analyze the spectrum of mutations in 34 HRR genes in prostate carcinomas (PCs) and study the relationship between HRR status and HRD. HRR mutations and HRD scores were examined by NGS in 1131 and 680 PCs, respectively. Pathogenic or likely pathogenic variants in HRR genes were detected in 216\/1131 cases (19.1%). HRD, defined by an HRD score cut-off of \u226542, was observed more frequently in HRR-mutated than in wild-type tumors (23\/120 (19.2%) vs. 29\/560 (5.2%), p &lt; 0.0001). The highest HRD scores were detected in PCs with biallelic inactivation of the BRCA2 or PALB2 genes, as well as in tumors with BRIP1 mutations. HRD was also occasionally seen in PCs with ATM, NBN, FANCM, BRCA1 and CDK12 alterations, but never in cases with CHEK2 mutations. HRD was significantly more associated with aggressive PC features than HRR mutations. The majority of CDK12-mutated tumors exhibited a distinct type of copy number variations (CNV)\u2013a tandem duplication phenotype. Our study suggests that the selection of PC patients for PARPi treatment requires a significant revision of existing attitudes towards tumor genetic profiling.<\/jats:p>","DOI":"10.3390\/ijms262411851","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:20:29Z","timestamp":1765210829000},"page":"11851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Complex Relationships Between Homologous Recombination Deficiency (HRD) Score and Mutational Status of Homologous Recombination Repair (HRR) Genes in Prostate Carcinomas"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-5186","authenticated-orcid":false,"given":"Aglaya G.","family":"Iyevleva","sequence":"first","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"},{"name":"Department of Medical Genetics, Saint Petersburg State Pediatric Medical University, Saint Petersburg 194100, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-7728","authenticated-orcid":false,"given":"Svetlana N.","family":"Aleksakhina","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-1609","authenticated-orcid":false,"given":"Anna P.","family":"Sokolenko","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"},{"name":"Department of Medical Genetics, Saint Petersburg State Pediatric Medical University, Saint Petersburg 194100, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina A.","family":"Otradnova","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa S.","family":"Nikitina","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9410-9009","authenticated-orcid":false,"given":"Kira A.","family":"Kashko","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3206-2871","authenticated-orcid":false,"given":"Maria V.","family":"Syomina","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna D.","family":"Shestakova","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2396-6540","authenticated-orcid":false,"given":"Ekaterina S.","family":"Kuligina","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3335-872X","authenticated-orcid":false,"given":"Natalia S.","family":"Morozova","sequence":"additional","affiliation":[{"name":"N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Popov","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Clinical Hospital, Saint Petersburg 194044, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel V.","family":"Vyazovcev","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Clinical Hospital, Saint Petersburg 194044, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana Y.","family":"Luchkova","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Clinical Hospital, Saint Petersburg 194044, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksey S.","family":"Peremyshlenko","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Clinical Hospital, Saint Petersburg 194044, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timur 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Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana N.","family":"Shkodenko","sequence":"additional","affiliation":[{"name":"Stavropol Regional Oncological Clinic, Stavropol 355047, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demyan V.","family":"Gubarev","sequence":"additional","affiliation":[{"name":"Stavropol Regional Oncological Clinic, Stavropol 355047, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandr V.","family":"Dzyuba","sequence":"additional","affiliation":[{"name":"Stavropol Regional Oncological Clinic, Stavropol 355047, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina Y.","family":"Povorina","sequence":"additional","affiliation":[{"name":"Tula Regional Oncological Clinic, Tula 300039, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna V.","family":"Agaeva","sequence":"additional","affiliation":[{"name":"Arkhangelsk Regional 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Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya V.","family":"Prokudina","sequence":"additional","affiliation":[{"name":"Kaliningrad Regional Oncological Clinic, Kaliningrad 236016, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya A.","family":"Butunina","sequence":"additional","affiliation":[{"name":"Saratov Regional Oncological Clinic, Saratov 410053, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksey M.","family":"Belyaev","sequence":"additional","affiliation":[{"name":"N.N. 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