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Abstract
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Introduction. Alteration of p53 function is a driving event in high-grade serous ovarian cancer (HGSOC). There are two main functional types of TP53 mutations: inactivating mutations associated with loss of gene expression (loss-of-function, LOF) and substitutions that confer novel oncogenic functions to p53 (gain-of-function).
Aim. To investigate whether the type of TP53 mutations (missense mutations in the DNA-binding domain (DBD)) affects the regrowth of micrometastases in the absence of cytotoxic exposure and thus the duration of the platinum-free interval (PFI) in patients with HGSOC.
Materials and Methods. The duration of PFI was analyzed in 60 HGSOC patients treated at the N.N. Petrov NMRC of Oncology between 2017 and 2023. The study included patients with known BRCA1/2 status who had completed adjuvant platinum-based therapy and were disease-free at the end of treatment. Somatic TP53 mutations were detected by next-generation sequencing.
Results. In BRCA1/2-associated cancers, significant differences in PFI duration were observed between patients with LOF and DBD TP53 mutations (median PFI 55.9 (95 % CI 12.5-99.4) and 11.5 (95 % CI 3.4-19.6) months, respectively (p = 0.04)). PFI > 12 months was observed more frequently for LOF mutations than for DBD missense mutations (10/11 [91 %] vs. 8/17 [47 %], p = 0.04). No such difference was observed in sporadic cancers.
Conclusion. In BRCA1/2-associated ovarian cancer, the type of TP53 mutations correlates with the duration of PFI and the frequency of achieving PFI>12 months. Analysis of the p53 status in HGSOC may improve the possibilities for personalized treatment of ovarian cancer.
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