Utility of Next-Generation Sequencing in Renal Neoplasia, Including Tumors With Clear Cytoplasm and Rare Phenotypes (ELOC/MITF Alterations and Mismatch Repair Deficiency)

作者：Michael McCarthy, Antonina Wojcik, Emily G. Barr Fritcher, Burak Tekin, Wei Shen, Hussam Al-Kateb, Surendra Dasari, Peter C. Lucas, Kingsley Ebare, Jordan Reynolds, Melissa L. Stanton, Aditya Raghunathan, Rumeal D. Whaley, Lori A. Erickson, Loren Herrera Hernandez, Rafael E. Jimenez, Brian A. Costello, Aaron Potretzke, Stephen A. Boorjian, Vidit Sharma, Bradley C. Leibovich, John C. Cheville, Benjamin R. Kipp, Sounak Gupta · 发表于：Mayo Clinic Proceedings · 年份：2026 · DOI：10.1016/j.mayocp.2025.11.003 · 被引用次数：1 · 研究领域：Renal cell carcinoma treatment、Cancer Genomics and Diagnostics、Renal and related cancers

OBJECTIVE: To define the clinical utility of next-generation sequencing (NGS) of renal tumors, including carbonic anhydrase 9-positive renal neoplasia with clear cell features (ccRCN) that include ELOC (for expansion of gene symbols, use search tool at www.genenames.org) and MTOR/TSC1/TSC2-mutated renal cell carcinoma (RCC) with fibromyomatous stroma (ELOC-RCCfms and M/TSC-RCCfms, respectively), as these tumors often have overlapping features. PATIENTS AND METHODS: Renal tumors (n=234) diagnosed between August 1, 2021, and June 15, 2025, were submitted for genomic profiling using Clinical Laboratory Improvement Amendments-validated 515-gene (n=30), 30-gene (n=175), and smaller (<5 gene, n=29) next-generation sequencing panels. Available histologic and NGS data was reviewed to render a final integrated diagnosis and determine clinical utility. RESULTS: Next-generation sequencing was requested solely for diagnostic indications in most cases (209 of 234 [89%]), with 66% of cases (154 of 234) showing a clinically impactful genomic profile. The highest utility was among ccRCN and high-grade RCC/RCC, type not otherwise specified (NOS) in which only 8 of 79 (10%) and 17 of 57 (30%) remained unclassifiable, respectively. Some rare phenotypes included variants associated with hereditary disease, uncommon presentations, multiple driver alterations, mismatch repair deficiency (n=3), and rare MITF p.E318K alterations (n=3). The cohort of ccRCN included 12 ELOC-RCCfms (p.Y79C/S: 9 of 12; ...