Abstract 2191: Clear cell renal cell carcinoma molecular differences between Hispanic Americans and European Americans

Abstract

Abstract Background: Hispanic Americans (HAs) in Arizona have a heavy burden of renal cell carcinoma (RCC) presenting at a younger age at diagnosis with higher incidence and mortality rates than European Americans (EAs). However, HAs are underrepresented in RCC research, and tumor molecular characteristics in this population are unknown. We report preliminary findings from a study of molecular differences between HAs and EAs exploring the molecular basis of early-onset clear cell RCC (ccRCC). Methods: Clinical records of patients who underwent surgical treatment for RCC between 2011 and 2020 at the University of Arizona Department of Urology was reviewed. A total of 539 patients were identified, and paraffin embedded surgical specimens of a subset of patients with ccRCC were selected for this study. Three exons of VHL gene, the most commonly altered gene in ccRCC, were screened for somatic mutations in a total of 117 patients. Thirty-three patients were included for TempO-Seq analysis to correlate molecular subtype with demographic and clinicopathologic characteristics. Results: Among 117 patients, 55 somatic mutations in coding regions of VHL were found in 42 patients (35.9%). Nine patients had more than 2 somatic mutations. There were 37 substitutions, 14 deletions, and 4 insertions. There was one patient with a mutation of an intron variant that was a splice acceptor. Mutations in the coding regions were more common in EAs (40.9%) than HAs (31%), but the difference was not statistically significant (P=0.32). For moderate or high impact mutations, EAs had mutations at a significantly higher frequency than HAs (39.4% vs. 20.5%, P=0.04). Patients with high impact mutations tend to be diagnosed before the age of 50 (37.5%) compared to patients without high impact mutations (23.9%). We were able to assign 32 out of 33 patients into molecular subtypes (ccA and ccB). Molecular subtype could not be assigned to one HA patient with high grade and advanced stage ccRCC. Compared to patients with ccB subtype, patients who had ccA subtype were younger (mean age of 52.2 vs. 61.4) and tend to be obese (55.6% vs. 28.6% body mass index ≥30). Molecular subtype, ccA, was more common in HAs than EAs (64.3% vs. 41.2%), but this difference was not statistically significant. Conclusion: Somatic mutations within the VHL gene often altered in early during ccRCC pathogenesis were less common in HAs, but ccA associated with early age of diagnosis and obesity was more common in HAs. Impact: HAs and EAs have different molecular basis of early-onset ccRCC which may impact clinical managements. Citation Format: Yuliang Chen, Karleen M. Meiklejohn, Nathan Ellis, Erika R. Bracamonte, Benjamin R. Lee, Ken Batai. Clear cell renal cell carcinoma molecular differences between Hispanic Americans and European Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2191.