{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:06:22Z","timestamp":1767909982482,"version":"3.49.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> A subset of renal cell carcinoma (RCC) cases occur because of a hereditary predisposition. However, the prevalence and profiling of germline alterations in RCC have not been fully characterized. Additionally, clinicopathologic factors associated with pathogenic or likely pathogenic (P\/LP) germline variants in patients with RCC remain poorly understood. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> A retrospective analysis of patients with RCC who underwent genetic evaluation was performed. The frequency of P\/LP germline variants and genes was evaluated in this cohort. The association between genetic testing outcomes and clinicopathologic features was also assessed. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of 321 patients with RCC who had germline testing were identified. Within this cohort, 42 patients (13.1%) had P\/LP variants. Genes with the most frequent germline mutations were FLCN (n = 10, 3.1%), SDHB (n = 4, 1.2%), VHL (n = 4, 1.2%), MLH1 (n = 3, 0.9%), and CHEK2 (n = 4, 1.2%). Among patients with P\/LP variants, 19 (45.2%) had a potentially targetable mutation. The presence of bilateral or multifocal tumors was associated with P\/LP variants ( P = .0012 and P = .0098, respectively). Patients who had targeted gene testing had higher rates of P\/LP variants compared with multigene panel testing ( P = .015). Age and family history of cancers (RCC and non-RCC) did not have any statistically significant association with germline testing outcomes. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Among patients with RCC, unselected for a known familial predisposition, 13.4% had P\/LP variants. Almost half of patients with P\/LP variants had a potentially targetable mutation. Targeted gene panel testing is a feasible option for patients, particularly if syndromic features are present. Age and family history were not associated with P\/LP variants. Future studies are needed to optimize current genetic evaluation criteria to expand the detection of patients with RCC who may have germline mutations. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.23.00168","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T20:59:37Z","timestamp":1703192377000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Pathogenic Germline Mutational Landscape in Patients With Renal Cell Carcinoma and Associated Clinicopathologic Features"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-5501","authenticated-orcid":true,"given":"Charles B.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Knaus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 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