{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:02:10Z","timestamp":1779778930880,"version":"3.53.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"\n Background<\/jats:title>\n \n Prostate cancer (PCa) is the most common malignancy among men in the United Arab Emirates (UAE) and is often diagnosed at advanced stages with aggressive features. Germline mutations in DNA-repair genes, especially\n BRCA1<\/jats:italic>\n and\n BRCA2<\/jats:italic>\n , increase PCa risk, with\n BRCA2<\/jats:italic>\n conferring up to 8.6-fold and\n BRCA1<\/jats:italic>\n a 3.7-fold risk. The objective is to determine the prevalence, zygosity, and clinical significance of\n BRCA1\/2<\/jats:italic>\n mutations in high-grade PCa among UAE and Arab patients and describe their potential role in disease aggressiveness.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A retrospective analysis was performed on 40 archived formalin-fixed, paraffin-embedded prostate tissues (2011\u20132022), comprising 23 PCa and 17 benign prostatic hyperplasia (BPH). Targeted exon sequencing was performed. Variants were classified using ACMG\/AMP criteria using ClinVar and Varchat. Associations between mutation patterns, zygosity, and tumor grade were evaluated.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n BRCA1<\/jats:italic>\n mutations occurred in 47.5% of cases, all in exon 10, with 62.5% homozygosity; most frequent were c.794G&gt;A and c.721G&gt;A. BRCA2 mutations occurred in 55% of cases, mainly exon 11, with 68% homozygosity; c.5917A&gt;C and c.5908T&gt;A were most common. Homozygous mutations enriched in high-grade PCa (Grade Groups 3\u20135) suggested biallelic inactivation and homologous recombination repair deficiency. Several novel variants clustered in DNA repair domains, including\n BRCA1<\/jats:italic>\n coiled-coil and\n BRCA2<\/jats:italic>\n RAD51-binding.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our findings reveal a high prevalence of homozygous BRCA1\/2 mutations, with the majority had aggressive disease phenotypes. Therefore, support the potential utility of PARP inhibitors as molecularly targeted therapeutic alternatives to conventional chemotherapy in mutation-positive patients. Furthermore, the identification of novel population-specific variants underscores the urgent need for ethnicity-informed genetic screening protocols, facilitating earlier detection of hereditary risk and enabling informed treatment stratification in United Arab Emirates and Arab men with PCa.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcell.2026.1737736","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:02:29Z","timestamp":1779775349000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive BRCA1\/2 mutation landscape in prostate cancer in the UAE and Arab population"],"prefix":"10.3389","volume":"14","author":[{"given":"Zainab M.","family":"Al Shareef","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rula M.","family":"Al-Shahrabi","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorna Manasa","family":"Bhamidimarri","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcu","family":"Yener","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Bouzid","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa Mohamed","family":"Hamad","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Murad","sequence":"additional","affiliation":[{"name":"Department of Pathology, Al Qassimi Hospital","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Elbarkouky","sequence":"additional","affiliation":[{"name":"Department of Pathology, Al Qassimi Hospital","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Saheb Sharif-Askari","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyad","family":"Bendardaf","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Oncology Unit, University Hospital of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifat A.","family":"Hamoudi","sequence":"additional","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Division of Surgery and Interventional Science, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmood Y.","family":"Hachim","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City","place":["Dubai, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s00432-025-06188-9","article-title":"Genetic characterization of BRCA1 and BRCA2 variants in cancer and high-risk family screening cohorts in the UAE population","volume":"151","author":"Al","year":"2025","journal-title":"J. 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