{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:23:44Z","timestamp":1791897824999,"version":"4.3.4"},"reference-count":113,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Cancer Institute"},{"name":"National Institutes of Health"},{"name":"NIH Medical Research Scholar Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Molecular testing in renal cell carcinoma (RCC) has allowed for a better understanding of the biology of both sporadic and hereditary diseases, where genetic testing is currently recommended in the guidelines for a select population with risk factors. Historically, screening, surveillance, and management decisions were based solely on clinicopathologic data; however, we now know that molecular profiling can enhance decision making, altering the treatment plan, approach, or selection of systemic therapy and enhancing the delivery of precision oncologic care. Advances and the increasing availability of next-generation sequencing technologies have improved the identification of germline and somatic variants in key RCC-associated genes. Given the molecular heterogeneity of RCC, these modern methods can identify unique genetic events that occur in a single individual, allowing for distinction between a metachronous tumor from metastases. Separate four-tier systems have been proposed to categorize germline and somatic variants according to their clinical significance, which should be highlighted. Additionally, emerging technologies, such as liquid biopsy, show potential for enhancing precision oncology in RCC. With this said, challenges, such as variant interpretation, ethical considerations, and accessibility, persist. This review examines the molecularly defined RCC, genetic testing methodologies currently available, their current clinical applications, limitations, and future directions.<\/jats:p>","DOI":"10.3390\/curroncol32060359","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T07:38:15Z","timestamp":1750232295000},"page":"359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Molecular Genetics of Renal Cell Carcinoma: A Narrative Review Focused on Clinical Relevance"],"prefix":"10.3390","volume":"32","author":[{"given":"Braden","family":"Millan","sequence":"first","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Loebach","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-0805","authenticated-orcid":false,"given":"Ruben","family":"Blachman-Braun","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan H.","family":"Patel","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaskirat","family":"Saini","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Marston","family":"Linehan","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-2627","authenticated-orcid":false,"given":"Mark W.","family":"Ball","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhou, N., Bai, H., Zhang, Z., Yu, B., Zhao, H., Li, J., and Zheng, G. (2025). Global, regional, and national burden of kidney cancer and attributable risk factors in adults aged 65 years and older from 1990 to 2021 and projections to 2040. 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