Millan Braden, Loebach Lauren, Blachman-Braun Ruben, Patel Milan H, Saini Jaskirat, Linehan W Marston, Ball Mark W
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Oncol. 2025 Jun 18;32(6):359. doi: 10.3390/curroncol32060359.
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.
肾细胞癌（RCC）的分子检测有助于更好地理解散发性和遗传性疾病的生物学特性，目前指南建议对有危险因素的特定人群进行基因检测。从历史上看，筛查、监测和管理决策完全基于临床病理数据；然而，我们现在知道分子剖析可以改善决策，改变治疗方案、方法或全身治疗的选择，并加强精准肿瘤治疗的实施。下一代测序技术的进步和可用性的提高，改善了关键RCC相关基因中种系和体细胞变异的识别。鉴于RCC的分子异质性，这些现代方法可以识别单个个体中发生的独特基因事件，从而区分异时性肿瘤和转移瘤。已经提出了单独的四级系统，根据种系和体细胞变异的临床意义对其进行分类，这一点应予以强调。此外，新兴技术，如液体活检，显示出增强RCC精准肿瘤学的潜力。话虽如此，变异解读、伦理考量和可及性等挑战依然存在。本综述探讨了分子定义的RCC、目前可用的基因检测方法、它们目前的临床应用、局限性和未来方向。
