The frequency and spectrum of hereditary mutations in the TP53 gene in an extensive study involving Russian breast cancer patients

Introduction. Breast cancer is the most common tumor localization in heritable TP53-related cancer syndrome (hTP53rc), previously called «Li-Fraumeni syndrome». This syndrome is characterized by the occurrence of a hereditary mutation in the TP53 gene. We wanted to demonstrate the relatively high incidence of hTP53rc in the structure of hereditary breast tumors, as well as to present a correct algorithm for the diagnosis of TP53-associated breast cancer in the Russian population. Aim. To study the incidence and spectrum of hereditary mutations in the TP53 gene in breast cancer patients. Materials and methods. We studied 1726 samples from breast cancer patients using next generation sequencing (NGS) to detect hereditary mutations in the TP53, BRCA1/2 genes. The feature of this study was the creation of «enriched» sample collection ― all samples from patients with any mutations in the BRCA1/2 genes were excluded from sample group using a special algorithm. CHEK2, NBS1, and BLM genes in 1322 from 1726 samples were additionally tested by PCR for the most common mutations in the population: CHEK2 del5395 (del ex9-10), CHEK2 c.444+1G>A [IVS2+1G>A], CHEK2 1100delC, NBS1 657del5, BLM p.Q548X [c.1642C>T]. Such a technique was used for detecting the carriership of double mutations and could make it possible to assess the features of the clinical manifestations of such situations in case of their detection. Usage of an algorithm based on NGS with the study of several genes made it possible to exclude samples with mutations and form a final sample group by which the occurrence of hTP53rc was calculated. Results. The occurrence of hTP53rc in the formed sample was 10/1494, which is 0.67%. Conclusion. The frequency of hTP53rc in the Russian population is obviously insufficiently estimated. The contribution of hTP53rc to the structure of hereditary breast cancer should be taken into account.