Worldwide, breast cancer (BC) is the most commonly diagnosed type of cancer in women and the leading cause of cancer-related death [1]. BC is a heterogeneous disease, which differ biologically among different patients and even within each individual tumor, therefore a major goal of improved classification of BC subtypes, is to stratify patient populations. Advanced in molecular characterization of tumors not only improve classification, but also point directly to molecular mechanisms that lead to different therapeutic responses [2]. Aim of this study was to identify clinicopathological and potential molecular/genetical predictors of breast cancer.
A total of 24 female BC patients form National Cancer Institute were included in this study. Six genes: TP53, CASP8, MTHF, MDM2, MDM4 and CCR5 were selected based on their mutation frequency and significance for disease development. Next generation sequencing (NGS) technology was applied for genomic profile analysis of BC. All identified mutations were validated by reviewing the results with Integrative Genomics Viewer (IGV). All identified genetic changes were classified as pathological, drug-responsive, benign, and variant of uncertain significance (VUS). Though, ClinVar is the major database used in clinical practice, mutations rated as VUS were additionally checked in other databases.
130 mutations were identified in breast tumor samples (24/24 patients). Non-pathological changes accounted for 77.7% of all detected mutations. Among them, benign gene sequence changes were the most common (62.3%). Pathological/likely pathological mutations accounted for 8.4% of all variants detected. TP53 had the greatest variety of genetic changes. Two VUS of TP53 gene were identified as likely pathological by COSMIC and VARSOME databases. CASP8 and MTHFR genes also showed a high frequency of changes, but no pathological mutations were detected. We did not find any associations between presence of pathological changes and clinical-demographic characteristics of patients.
In conclusion, this genetic profiling revealed that TP53 gene has the greatest variety of mutations and the largest number of pathological variants in BC patients in this study. However, more research is needed to determine connection between genetic changes and clinical manifestations of disease and to use the results in molecular/genetic classification of tumors.