Tumor genomic landscape in younger compared to older patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC).

Abstract

373 Background: Renal cell carcinoma is predominant in 6th to 8th decade of life. Younger pts are more likely to have symptomatic tumors on presentation but with favorable pathological features and disease specific survival (PMID: 17092632). Herein, we hypothesized that the genomic landscape for pts with onset of renal cell cancer at a younger age is distinct from those with late age of onset. Methods: In this IRB-approved retrospective study, pts with mccRCC and tumor comprehensive genomic profiling (CGP) available from a CLIA-certified laboratory were evaluated. Among these, the pts in the first and fourth quartiles of age were included in this study. Variants of unknown significance and gene with alterations (GA) present in less than 5% of pts were excluded from the analysis. A chi-square test was used to compare gene aberration frequency and p-values were adjusted for false discovery rate (FDR) using Benjamini-Hochberg (BH) correction. The median number of genomic aberrations per pt was compared using Wilcoxon rank-sum test. Results: 78 pts were eligible and included: first quartile (Range: 25-53 years; n=54) and fourth quartile (Range: 68-77 years; n=38); male vs female: 30/13 vs 20/15. The genomic aberrations observed in both groups is listed in the table. GA in VHL and PBRM1 were the most commonly observed in both groups . Most commonly observed genomic alterations in first quartile was TP53, BAP1, CDKN2B and TSC1; and fourth quartile of age was SETD2, TSC1, KDM5C and TP53. Tumor mutation burden and the frequency of gene aberrations was similar across both the cohorts. Conclusions: In these hypothesis generating data, there was no significant difference in prevalence of targetable genomic aberrations, tumor mutational burden and frequency of genomic alterations in younger vs older pts with mccRCC. The numerically higher GA in KDM5C and SETD2 (both of which contribute to epigenetic dysregulation) in older pts warrant interrogation in a larger data set. Future directions may include the investigation of epigenomic changes and transcriptomic profiling. Detailed genomic landscape of these pts will be presented in the meeting.[Table: see text]