Genomic landscape of metastatic clear cell renal cell carcinoma (mccRCC): A retrospective real-world analysis from Flatiron Health (FH)-Foundation Medicine, Inc. (FMI) clinico-genomic database (CGDB).

• DOI: 10.1200/jco.2024.42.16_suppl.4552
• Publication Date: 2024-06-28T20:30:31Z
• Authors: Mimma Rizzo; Gaetano Pezzicoli; Camilla Porta; Massimiliano Povero; Lorenzo Pradelli; Emilia Sicari; Valentina Sara Ba...; Camillo Porta
• Keywords: Foundation (evidence)

4552 Background: Although the genomic landscape of mccRCC has been already documented in literature, previous clinico-genomic studies have constrained by small sample sizes, or a narrow focus on specific genes. In this large-scale study, we aimed at investigating real-world frequency and co-occurrence alterations (GAs) detected samples. Methods: This study used nationwide (US-based) de-identified FH-FMI CGDB. The data originated from approximately 280 US cancer clinics (~800 sites care). Eligible patients (pts) were adults diagnosed with mccRCC, FH-EHR records between January 1, 2011 December 31, 2022. GAs identified same time span via comprehensive profiling using FMI tests tumor tissue blood Co-occurrence mutual exclusivity assessed Fisher's exact test, multiple testing correction. Clustering analysis was performed gene network graph derived significant interactions. Results: Out 1,409 pts renal cell carcinoma, 923 (65.5%) considered, median age diagnosis metastatic disease 61 years (IQR: 54-69). majority male (70.3%) white (71.1%). Nearly 89% (822) received systemic therapy, number 2 treatment lines 1-4). A total 958 samples sequenced, which 92.2% tissue, 7.8% blood. (81.1% short variant, 17.1% copy 1.8% rearrangement) found 246 different genes, mutated genes per 3 2-5), while 22 (2.4%) pts, no detected. VHL (69.7%), PBRM1 (39.9%), SETD2 (24.2%), CDKN2A (19.0%), BAP1 (15.6%), CDKN2B(14.8%), TP53 (14.1%), KDM5C (13.5%), PTEN (11.2%), TERT (8.7%) top-10 Tumor Mutational Burden (TMB) evaluated 639 samples, value 2.6 mut/Mb; 1.6% only tumors studied had high TMB. 796 examined for microsatellite instability (MSI), 0.6% harbored MSI-intermediate, none showed MSI-high. revealed 32 CDKN2A/B significantly associated MTAP, BAP1, NF2, enriched VHL, SETD2, KDM5C, MTOR. TSC1co-occurred TERT, TP53, VHL.Three clusters co-occurring identified: (1) PBRM1, MTOR, NFE2L2; (2) TSC1, TERT; (3) CDKN2A, CDKN2B, ARID1A. Mutually exclusive patterns observed cluster 1 Notably, mutually PBRM1. Conclusions: is largest mccRCC. We whose prognostic/predictive will be object future research.