Hello, everyone. My name is Rodrigo. I am a PhD student at Barreiros Cancer Hospital from Brazil. And today, I'm presenting my work entitled Clinical Pathological and Genetic Answers to Impact of GP53 Mutations in Brazilian Lung Adenocarcinoma Patients. I do not have any financial relationships to disclose. And I'd like to thank our colleagues to collaborate with this work. The GP53 gene is the most mutated in lung adenocarcinoma and plays a crucial role in maintaining genome stability. And the presence of mutations may lead to different biological effects. So mutations may be classified as disruptive and non-disruptive mutations. Data about the frequency and clinical impact to data in admitted lung adenocarcinoma populations are scarce, mainly in Brazil. So we aim to describe the frequency of GP53 mutations and their association with clinical pathological and genetic answer background data in lung adenocarcinoma patients from Brazil. So we included 446 NESELC patients diagnosed at Barreiros Cancer Hospital. From these patients, we selected 366 lung adenocarcinoma patients that were routinely evaluated for GP53 molecular status. The mutations were classified as disruptive and non-disruptive mutations. We also evaluated the genetic answer background for a subset of these patients. We also performed in silico analysis with lung adenocarcinoma patients from TCGA online data set. We included 547 patients with GP53 mutational status and self-reported pink color data available. For statistical analysis, we described that the frequency of mutations and patient's features followed by association with the presence of GP53 mutations. We also evaluated the overall survival of patients and the risk of death for these patients. Briefly, we had 366 lung adenocarcinoma patients, 22 scomal cell carcinoma patients, and 58 patients with other types of NESELC. About GP53 mutations, 60% of lung adenocarcinoma patients were harboring GP53 mutations, while in the scomal cells carcinoma and other types, 81% of patients were harboring these mutations. From lung adenocarcinoma patients, 31% mutated only for GP53 gene, while 29% were mutated for GP53 gene and EGFR or KRAS gene concomitantly. From GP53 mutated patients, we identified 248 mutations and most of them were located in the DNA binding domain at codons 273 and 337. We also evaluated the association of disruptive and non-disruptive mutations with clinical pathological feature. We observed that GP53 mutations were associated with younger age at diagnosis, self-reported non-life patients, and tobacco exposure. We also observed that GP53 mutations were associated with worse performance status and metastases at diagnosis. We also evaluated the genetic answer background for a subset of these patients and divided into tertiary. After this classification, we observed that GP53 mutations were associated with a higher African genetic answer tree, lower European genetic answer tree, and intermediate Native American genetic answer tree. In the multinomial logistic regression, we observed that disruptive mutations were associated with younger age at diagnosis, current smoker patients, central nervous system metastasis at diagnosis, and higher African answer tree background. While non-disruptive mutations were independently associated with quitter and current smoker patients, central nervous system metastasis at diagnosis, higher African answer tree background, and patients with no mutations in the KRAS gene. We also analyzed the GP53 associations in the PCGA data set. And we also observed the association between mutations in the younger age at diagnosis and black African patients. About overall survival, we observed that GP53 mutated patients had shorter overall survival and also disruptive patients had shorter overall survival compared with non-disruptive patients. However, when we perform a Cox regression analysis, GP53 mutations were not an independent factor associated with the risk of death. In our series, worst performance stats in metastatic diagnosis were associated with a higher risk of death, while GPR mutations were associated with a lower risk of death. In conclusion, our study reported that GP53 mutations are frequently found in Brazilian legatino carcinoma patients and associated with worse overall survival. Thank you for your attention.

GP53 mutations

lung adenocarcinoma

Brazil

frequency

impact