Presentation Authors: Mark Ball*, Christopher Ricketts, Cathy Vocke, Laura Schmidt, Martin Lang, Caitlin Drew, Deborah Nielsen, Lindsay Middleton, Marston Linehan, Bethesda, MD
Introduction: Renal cell carcinoma (RCC) caused by a known germline genetic alteration accounts for 5-8% of all RCC cases. Some patient populations may be enriched for more frequent germline alterations, including patients with early onset (EO) (age of diagnosis < 46) RCC, bilateral multifocal (BMF) RCC, or familial renal cancer (FRC). We sought to characterize the frequency of positive germline mutation testing in these potentially enriched populations.
Methods: Patients treated at our institution from 2016-2018 who had a germline panel for known hereditary RCC genes were analyzed. Patients with a personal or family history of a known hereditary syndrome as well as patients with no known history of a solid kidney tumor were excluded. Comparative statistical analysis and multivariate logistic regression were used to determine which groups of patients have the highest frequency of positive germline alterations.
Results: Overall, 207 patients had hereditary RCC gene panel testing. Of these 179 had at least 1 feature from a potentially enriched population, including 92 with EO, 113 BMF, and 54 FRC (Figure 1). Panel results were positive in 36 patients (17.4%), negative in 141 (68.1%), and had a variant of uncertain significance (VUS) in 30 (14.5%). The number of enriched features increased the proportion of positive results; patients with no features had positive results in 7.1% of cases, 1 feature 12.8%, 2 features 21.7% and 3 features 70%. In a multivariate logistic regression model controlling for all risk factors, the odds ratios for positive germline alterations were FRC 4.8, p < 0.001; BMF 2.5, p = 0.03, EO 1.5 p = 0.3.
Conclusions: EO, BMF, and FRC are enriched populations with more frequent positive germline RCC alterations than the patients with RCC without one of these features. These findings support germline gene panel testing in these populations.