Sequencing of TP53 R175H/G mutations in cancer cells.
We explored the relationship between TP53 missense mutations and platinum resistance in patients with high-grade serous ovarian cancer (HGSOC). Results suggest that mutations in specific p53 domains contribute to the acquired cisplatin resistance. Notably, at the R175 hotspot, two distinct variants-R175H and R175G-were identifield in relapsed resistant group. The p53R175G mutation showed heightened resistance to cisplatin and increased tumor migration, displaying insensitivity to drugs targeting p53R175H. This suggests that targeted therapies aimed at a specific amino acid may not be effective against other mutations at the same site. While both p53R175H and p53R175G demonstrate acquired resistance and migratory capabilities, their cofactors and functional mechanisms may differ. To further investigate these mechanisms, we employed transcriptome sequencing.