Somatic mutation profiles of metastatic non–clear-cell renal cell carcinoma (nccRCC) vary by subtype, and analyzing somatic and germline mutations and microsatellite instability (MSI) may reveal clinically actionable mutations in a proportion of patients with advanced disease, according to a recent report published in JCO Precision Oncology. Among all RCC cases, approximately 20% are nccRCC, which includes subtypes that are highly heterogeneous. Since nccRCC has limited sensitivity to conventional agents targeting vascular endothelial growth factor and mammalian target of rapamycin, a strong need for better therapies exists, and characterizing genomic variations may aid in this quest. Carlo and colleagues retrospectively analyzed tumor tissue from 116 patients with metastatic nccRCC. Among these patients, 57 had de novo metastatic disease (49%), and 59 had localized disease that later metastasized (51%). The subtype classifications were highly varied (35% unclassified, 22% papillary, 15% chromophobe, 11% translocation associated, and 16% other). The team used OncoKB classification to annotate individual mutations for their therapeutic potential and found that 13% of all tumors harbored potentially actionable somatic mutations. They also explored the efficacy of targeted therapies in patients who received treatment, and found that 33% of patients had an objective response and an additional 25% achieved stable disease. These are very promising findings and point toward more personalized medicine in these subtypes of nccRCC, the authors noted.
Source: Cancer Network
