Abstract A042: Hotspot mutations difference between gender and early- and late-onset lung adenocarcinoma patients

Abstract In this study we used mutations data from 22,300 patients with lung adenocarcinoma (LUAD) to test the frequency of hotspot mutations. We found that TP53 R158 and R273 mutations were more frequent in AA females, while TP53 R158 and R248 mutations were more prevalent in AA males. In Asian population, we found that TP53 R273 mutations were frequent in females and R273 and R248 mutations were more prevalent in males. In the White population, we found that TP53 R273, R248, and G245 mutations are frequent in females, and TP53 R273 and R248 mutations were more often in male lung adenocarcinoma patients. R248 mutations were common in AA, Asian and White males patients, but TP53 hotspot mutations were variable among AA, Asian and White female populations. When we compared the distribution of TP53 hotspot mutations between the early- and late-onset female AA LUAD patients, we found that TP53 Y220 mutations were frequent in early onset patients andTP53 R273 mutations were more often in late-onset cases. In male AA patients, we found that TP53 R249W and R158G/L mutations were more prevalent in early-onset, and R249M/S/G, R158 L/P, and R273 mutations were more frequent in late-onset LUAD patients. In Asian females, we found TP53 R273C/H/L mutations were more frequent in early onset, while R273H/C/L/P/S mutations were frequent in late-onset cancer. In Asian males, we found TP53 R273L/C/H/P/S mutations were more prevalent in early-onset, while R273 and R248 mutations were the most frequent hotspot mutations in late-onset patients. In female White population, we found TP53 R248Q/W mutations were more often in early-onset patients, while R273C/H/S/G mutations were more frequent in late-onset LUAD patients. In male White patients, we found that TP53 R248W and R273P mutations were more frequent in early age of onset, when R273S/G and R248Gfs*97/P hotspot mutations were more prevalent in late-onset LUAD patients. Our analysis provides evidence that even if the same hotspot mutations exist among the groups, mutations were still different. Our data indicates that the distribution and frequency of TP53 hotspot mutation noticeable female and male as well as between early- and late-onset of lung adenocarcinoma patients. Citation Format: Musaffe Tuna, Christopher I. Amos, Gordon B. Mills. Hotspot mutations difference between gender and early- and late-onset lung adenocarcinoma patients [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A042.