{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:04Z","timestamp":1760060584463,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turkish Pediatric Oncology Group (TPOG) under the 2022 Research Projects Support Program","award":["1591","DEU.HSI.PhD-2015970051"],"award-info":[{"award-number":["1591","DEU.HSI.PhD-2015970051"]}]},{"name":"Dokuz Eyl\u00fcl University","award":["1591","DEU.HSI.PhD-2015970051"],"award-info":[{"award-number":["1591","DEU.HSI.PhD-2015970051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin is an alkylating chemotherapeutic drug used in the treatment of many pediatric solid tumors, and cisplatin ototoxicity is characterized by sensorineural, bilateral, irreversible, and progressive hearing loss. The aim of this study is to identify biomarkers that may serve as predictors of cisplatin-induced ototoxicity in pediatric cancers. In our preliminary study, patients with severe hearing loss were analyzed using the comparative genomic hybridization (CGH) method. Mutations were identified in the following genes: ADAM6, SIX3, GNAS, NDUFV1, H19, DEFA4, and ZIM2. Based on these data, we aimed to investigate the mutation status of these candidate genes in a larger population of pediatric cancer patients treated with cisplatin. DNA samples were extracted from the mononuclear cells of peripheral blood samples obtained from 82 patients. These genes were analyzed using the RT-PCR technique, and ototoxicity was assessed using the Brock and Muenster classifications. Hearing loss was detected in 28% of patients; 76.8% and 23.2% had mild and severe hearing loss, respectively. A significant correlation was found between ZIM2 gene amplification and the presence of ototoxicity (rho = 0.461, p = 0.003), especially in advanced-stage cancer patients with severe hearing loss (rho = 0.38, p = 0.017). Our findings suggest that ZIM2 is a promising biomarker for predicting cisplatin ototoxicity.<\/jats:p>","DOI":"10.3390\/ijms26188880","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T09:07:15Z","timestamp":1757668035000},"page":"8880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determination of a New Biomarker at the Level of Gene Alteration in Cisplatin Ototoxicity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-7140","authenticated-orcid":false,"given":"Deniz","family":"K\u0131zmazo\u011flu","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Institute of Oncology, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aylin","family":"Erol","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Institute of Oncology, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tekincan \u00c7a\u011fr\u0131","family":"Akta\u015f","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Institute of Oncology, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y\u00fcksel","family":"Olgun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-8151","authenticated-orcid":false,"given":"Ay\u015fe Banu","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Izmir University of Economics, Izmir 35330, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zekiye","family":"Altun","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Institute of Oncology, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7658-5565","authenticated-orcid":false,"given":"Safiye","family":"Akta\u015f","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Institute of Oncology, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nur","family":"Olgun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Institute of Oncology, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"},{"name":"Ac\u0131badem Kent Hospital, Kars\u0131yaka, Izmir 35630, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1200\/OP.22.00710","article-title":"Cisplatin-Induced Ototoxicity: A Concise Review of the Burden, Prevention, and Interception Strategies","volume":"19","author":"Chattaraj","year":"2023","journal-title":"JCO Oncol. 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