Распространенность клинически значимых мутаций PIK3CA: результаты анализа опухолевых образцов 1452 пациентов российской когорты

Prevalence of clinically significant PIK3CA mutations: results of tumor sample analysis from 1452 patients in a Russian cohort

PIK3CA mutations represent one of the most frequent driver events in malignant neoplasms, particularly in hormone-dependent breast cancer. Activation of the PI3K/AKT/mTOR pathway promotes tumor growth, drug resistance, and poor prognosis. Objective. To assess the frequency and spectrum of clinically significant mutations in the PIK3CA gene in various types of malignant neoplasms in patients from a Russian cohort. Material and methods. The study included sequencing data from 1,556 tumor samples (1,452 patients) that underwent molecular genetic testing at the National Medical Research Radiology Center of the Ministry of Health of the Russian Federation between 2022 and 2025. Targeted panels and whole-exome sequencing with a coverage depth of 200—1000× were used. Analysis was performed according to GATK Best Practices; annotation was conducted using VEP and OpenCaravat; statistical analysis was carried out in Python. Results. PIK3CA mutations were identified in 12.1% of all samples, with a frequency of 26.8% in breast cancer and 5.1% in other tumor types (p<10–⁶). The most common variants were H1047R (29%), E545K (19.9%), and E542K (9.9%). Co-mutations were most frequently observed with TP53 (38.8%) and less often with KRAS and PTEN. Conclusion. The PIK3CA mutation spectrum in the Russian cohort generally corresponds to global data and confirms the significance of the PI3K/AKT/mTOR pathway as a key target for precision therapy, especially in hormone-dependent tumors. © 2025, Media Sphera Publishing Group. All rights reserved.