Abstract A024: Prognostic effects of different TP53 mutations in pancreatic ductal adenocarcinoma

Abstract Approximately, 70% of pancreatic ductal adenocarcinomas (PDACs) have mutations in the TP53 gene; however, it is still unknown if gain- or loss- of function mutations in TP53 provide differential prognostic value to guide therapy. To fill this gap, we assessed the potential effect of wild-type, missense (gain-of-function) and truncating (loss-of-function) TP53 mutations in patient survival, in two independent clinical cohorts (The Cancer Genome Atlas cohort=141, and the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets cohort=376 PDACs). We employed multivariable Cox proportional hazards regression models adjusting for patient demographic (age at diagnosis, sex, race/ethnicity) and tumor characteristics (presence of distant metastasis at diagnosis). Additionally, we conducted stratified analyses by the status of “druggable” (DNA repair gene mutations) and other driver mutations (SMAD4 and CDKN2A genes). We found that PDACs with missense TP53 mutations were associated with a worse patient survival compared to tumors with wild-typeTP53 (HR = 1.47, 95% CI: 1.00-2.17; p=0.051). Similarly, patients with truncating mutations in TP53 had a trend to worse OS (HR=1.11, 95% CI, 0.70-1.76; p=0.654) compared to patients with wild-type TP53, however, these associations were not significant. Furthermore, we found that mutations in DNA repair genes, SMAD4 and CDKN2A genes did not show any prognostic value. Our findings suggest that molecular characterization of specific TP53 mutations may help to determine differences in patient prognosis and potentially guide future clinical management of patients. Citation Format: Carlos M. Mejia Arbelaez, Xining Shan, Tseng Robert, Marie E. Robert, Xiaomei Ma, Luisa F. Escobar-Hoyos. Prognostic effects of different TP53 mutations in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A024.