Targeted Gene Panel Testing Can Assist Patients With RCC, Germline Mutations

While some cases of renal cell carcinoma (RCC) occur due to a hereditary predisposition, the prevalence and profiling of germline alterations in patients with RCC has not been distinguished, and the clinicopathologic features associated with pathogenic or likely pathogenic (P/LP) variants are poorly understood.

Researchers recently conducted a retrospective analysis of patients with RCC who received genetic evaluation to determine the connection between genetic testing outcomes and clinicopathologic features, as well as the frequency of P/LP germline variants and genes.

A total of 321 patients with RCC who had undergone germline testing were included in the analysis. P/LP variants were noted in 42 (13.1%) patients, with 19 (45.2%) of those patients possessing a potentially targetable mutation. Patients with P/LP variants were more likely to have bilateral or multifocal tumors (P=.0012 and P=.0098, respectively).

The genes with the most frequent germline mutations included 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%). Patients who underwent targeted gene testing had higher rates of P/LP variants compared with patients who received multigene panel testing (P=.015). Family history of cancer (RCC and non-RCC) and age were not significantly associated with germline testing outcomes.

In patients with RCC who did not have a familial predisposition to the disease, 13.4% had P/LP variants, and almost half of patients with P/LP variants had potentially targetable mutations. Family history and age were not associated with P/LP variants.

Targeted gene panel testing can serve as an option for patients if syndromic features are present. Further studies are needed to clarify the current understanding of genetic evaluation criteria to expand the detection of patients with RCC who may have germline mutations.