P70.02 Clinicopathological and Genetic Ancestry Impact of TP53 Mutations in Brazilian Lung Adenocarcinoma Patients

Abstract

TP53 is the most mutated gene in lung adenocarcinoma tumors. TP53 gene plays a crucial role in maintaining genome stability, and the presence of alterations in this gene may lead to uncontrolled cell proliferation and cancer. However, the frequency of TP53 mutation and its clinical impact in admixture lung adenocarcinoma populations, such as the Brazilian population, is unclear. Aim: To describe the frequency of TP53 mutations and their association with clinicopathological and genetic ancestry background data in lung adenocarcinoma patients in Brazil. We evaluated a retrospective FFPE series of lung adenocarcinoma (n=363) diagnosed at Barretos Cancer Hospital, Barretos, Brazil, between 2018 and 2020. TP53 mutational status was assessed by NGS (TruSight Tumor 15, Illumina). The genetic ancestry analysis was assessed on tumor DNA by a specific panel of 46 ancestry informative markers, and the ancestry proportions for Asian, African, European, and Native American was calculated. In accordance with the AJCC 7thedition, the following disease stage was present at diagnosis: I/II (n=51); III (n=43), and IV (n=245). We observed the presence of TP53 mutations in 59% (n=215) of cases. About 71.0% of mutations were missense variants and the majority were located in the DNA-binding domain of the TP53 gene (Figure1). Furthermore, the codon Arg273 was the most mutated (n=13), and the R337H variant (founder-effect in Brazil) was identified in 10 cases (4.65%). TP53 mutations were associated with younger age at diagnosis(p=0.006) quitter and current smokers(p=0.006 and p=0.001), and intermedium and high African genetic ancestry(p=0.012 and p<0.0001). TP53 mutated patients presented a significantly worse overall survival (14 months) compared to wild-type patients (22months) (p=0.024). The adjusted cox regression model showed TP53 mutational status(TP53m HR=1.15, p=0.386) was not independently associated with worse outcomes. Apart from, EGFR mutational status(EGFRm HR=0.44, p<0.0001), advanced disease at diagnosis(HR=15.78, p<0.0001), and PS ECOG at diagnosis(PS1 HR=2.25, p=0.032; PS2 HR=3.71, p=0.01; PS3/4 HR=5.91, p<0.0001) were independently associated with worse outcomes regardless of disease course. TP53 mutations are present in 59.0% in Brazilian lung adenocarcinoma patients. TP53 mutations are associated with younger patients, quitter and current smokers, patients with African genetic ancestry background.