Abstract 3400: Co-mutations in FGFR3 and CDKN2A in bladder cancer: a descriptive analysis

Abstract Introduction: Bladder cancer is the 9th most common cancer worldwide. Two key genetic alterations, in Fibroblast Growth Factor Receptor (FGFR3) and Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A), are known to contribute to its development. Interactions between these genes have been suggested in bladder cancer progression. However, limited data exists on patients' demographics with co-mutations in these genes. Methods: This retrospective study evaluates the patient demographics and survival analysis in patients with co-mutated CDKN2A and FGFR3 in bladder cancer. We utilized the cBioPortal MSK Cell Reports 2022 Database for Bladder cancer for our samples. We quantified our samples based on an FGFR3 mutation, CDKN2A mutation, co-mutation in FGFR3/CDKN2A, or wild-type mutation. Further associations of these mutations were tested with race, gender, smoking status, and cancer stage. Kaplan-Meier estimates for overall survival (OS) were compared for the mutational status and log-rank tests were used to compare survival curves. Statistical analysis was performed using Chi-square tests for categorical variables, and time to event analysis was performed using log-rank test. A p-value <0.05 was used for statistical significance. Results: We evaluated 1462 samples in our study. 139 patients had a co-mutated CDKN2A/FGFR3 (9.5%), 243 with FGFR3 alteration (16.7%), 184 with CDKN2A alteration (12.5), and 896 (61.2 %) with no alteration. There was a statistically significant difference in smoking status when stratified by mutational status: current or former smokers compiled 67.9% of the co-mutated CDKN2A/FGFR3 cohort, 59.6% in the FGFR3 group, 65.9% in the CDKN2A group, and 64.4% in the wild type group (p=0.010). 76% of patients were male, 26% were female, and 92% were of Caucasian race; no statistical significance was noted when stratified based on gender or race. When stratifying based on cancer stage, co-mutated CDKN2A/FGFR3 was most commonly seen in Stage I and IV bladder cancer. The 5-year survival probability for patients with co-mutated FGFR3/CDKN2A was 57.9%, compared to 60.9% in FGFR3 samples, 56.8% in CDKN2A samples, and 54.7% in the wild-type samples(p=0.261). Median OS was only reached for the wild-type mutation. Conclusions: Our retrospective study outlines the different population groups with aberrations in either FGFR3 or CDKN2A. Patients who were current/former smokers were more likely to have a co-mutated FGFR3/CDKN2A mutation. Patients with wild-type CDKN2A/FGFR3 fared worse when looking at median overall survival (77.4 months), and patients with co-mutated CDKN2A/FGFR3 had the best response (median OS not reached). One of the considerable limitations of this database is the homogeneity of the population, with the vast majority of patients being of Caucasian descent. We hope to evaluate further our bladder cohort of patients, where we have a diverse group of patients that may give us better insight into these alterations. Citation Format: Muhammad A. Shahid, Radhika Gutta, Sunita Ghosh, Nallasivam Palanisamy. Co-mutations in FGFR3 and CDKN2A in bladder cancer: a descriptive analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3400.