| Abstract [eng] |
Despite improving diagnostic tools, breast cancer (BC) remains the leading oncological disease in women. Inherited BRCA1/2 gene mutations increase the risk of BC by 70%, and TP53 mutations are found in 20–50% of all BC cases. In cancer cells, hypermethylation of tumor suppressor genes results in the silencing of gene function. Our study analyzed the influence of the inherited BRCA2 c.3847_3848delGT mutation on the progression of familial BC disease. TP53 mutations and hypermethylation of 17 genes with different functions in the cell were analyzed in sporadic BC. 10 of the 17 tested DNA methylation markers statistically significantly distinguished BC from control samples. During analysis of the highly heterogeneous and aggressive triple-negative (TN) subtype, we found MT1E and FILIP1L biomarkers specific to it, which were associated with tumor proliferation, poor differentiation grade, and TP53 mutations. In the survival analysis, a statistically significant association was found between hypermethylation of RUNX3 with MT1E and FILIP1L or all three genes together and patient survival. FILIP1L hypermethylation along with TP53 mutations were associated with poor disease outcomes. The study identified diagnostic and prognostic BC biomarkers that could facilitate timely tumor identification, and biological subtyping and enable the prediction of the progression of BC, prognosis of the response to treatment, and expand the possibilities of individualized BC therapy. |
