Approximately 10% of all breast cancer (BC) cases are familial and caused by inheritance of mutant BRCA1, BRCA2, or some other genes from the same DNA reparation pathway. Genetic counseling in families with cancer history is a powerful means for early cancer detection and active risk reduction through preventive interventions. This is the first report of the rare inherited BRCA2 frameshift-deletion mutation c.3847_3848delGT in one Lithuanian pedigree with the intense familial history of BC. Three BRCA2-positive blood relatives with BC of different biological types were identified in this pedigree with the same type mutation. All three cases were diagnosed with advanced stage ductal carcinoma. Markedly, polymorphic cells and numerous mitoses were identified in BC from the cases. Two patients from the family were diagnosed with the triple negative tumors, while one case had early onset of the hormone positive BC. Despite the variation in clinical and biological presentation of BC, all cases showed a good response to conventional treatment. In conclusion, the strong influence of BRCA2 mutation on the onset of BC of various biological types reveals the complexity of genetic counselling in families with BC history.

The acetylation of histones and transcription factors plays a crucial role in cell functional activity. Balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs) is closely related to diverse cellular processes, including differentiation, proliferation, and apoptosis. Expression of different classes of HDACs is strictly dependent on the cell type, and differentiated cells possess different members of the HDAC family. In our study, we employed mesenchymal stem-like cells (MSC) derived from human exfoliated deciduous teeth. Expression of HDACs at mRNA level was analysed using the RT-PCR method. Next, we have assessed the protein levels of different classes of HDACs and their localization within the cell. The cytoplasm and nuclear fractions of cell lysates were subjected to western blot analysis. Since the functional activity of class II HDACs is determined by their shuttling between the nucleus and the cytoplasm, we have analysed the subcellular localization of HDAC4 in response to the wellknown activators of differentiation, i. e. bone morphogenetic protein 2 (BMP-2) and phorbol 12-myristate-13-acetate (PMA), using fluorescent confocal microscopy. Our results suggest that class I and II HDAC family members are expressed and produced in MSC-like cells. The predicted HDAC4 translocation from the cell nucleus was not induced by PMA or BMP-2 in our model. However, our findings open new insights into a possible targeting for HDACs in future transcription activations / derepression studies.

This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions.