ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

The analysis of transcriptomic signature of TNBC-searching for the potential RNA-based predictive biomarkers to determine the chemotherapy sensitivity.

Neoadjuvant chemotherapy is the foundation treatment for triple-negative breast cancer (TNBC) and frequently results in pathological complete response (pCR). However, there are large differences in clinical response and survival after neoadjuvant chemotherapy of TNBC patients. The aim was to identify genes whose expression significantly associates with the efficacy of neoadjuvant chemotherapy in patients with TNBC. Transcriptomes of 46 formalin-fixed paraffin-embedded (FFPE) tumor samples from TNBC patients were analyzed by RNA-seq by comparing 26 TNBCs with pCR versus 20 TNBCs with pathological partial remission (pPR). Subsequently, we narrowed down the list of genes to those that strongly correlated with drug sensitivity of 63 breast cancer cell lines based on Dependency Map Consortium data re-analysis. Furthermore, the list of genes was limited to those presenting specific expression in breast tumor cells as revealed in three large published single-cell RNA-seq breast cancer datasets. Finally, we analyzed which of the selected genes were significantly associated with overall survival (OS) in TNBC TCGA dataset. A total of 105 genes were significantly differentially expressed in comparison between pPR versus pCR. As revealed by PLSR analysis in breast cancer cell lines, out of 105 deregulated genes, 42 were associated with sensitivity to docetaxel, doxorubicin, paclitaxel, and/or cyclophosphamide. We found that 24 out of 42 sensitivity-associated genes displayed intermediate or strong expression in breast malignant cells using single-cell RNAseq re-analysis. Finally, 10 out of 24 genes were significantly associated with overall survival in TNBC TCGA dataset. Our RNA-seq-based findings suggest that there might be transcriptomic signature consisted of 24 genes specifically expressed in tumor malignant cells for predicting neoadjuvant response in FFPE samples from TNBC patients prior to treatment initiation. Additionally, nine out of 24 genes were potential survival predictors in TNBC. This group of 24 genes should be further investigated for its potential to be translated into a predictive test(s).

Relationship in development of malocclusions to polymorphisms of selected vitamin D receptors.

BACKGROUND: The development of malocclusion is related to various factor, many of which are still not fully explained. The steroid hormone, 1,25-dihydroxyvitamin D3, has pleiotropic effects. It plays a key role in skeletal metabolism and the control of cell repair by attaching to the nuclear vitamin D steroid receptor (VDR). This vitamin affects bone turnover through the processes of bone tissue formation and resorption via its action on cells of the osteoblastic and osteoclastic lineage, exerts a modulating effect on the immune system, and is involved in the regulation of cell proliferation and differentiation. The role of vitamin D3 (VD3) and its receptor polymorphisms is a rarely studied topic in dentistry. Due to the proven influence on bone turnover processes and immune responses, the main research topic is its relation to periodontal diseases, but so far, its role in the formation and development of malocclusions has not been assessed. OBJECTIVES: This study aimed to assess the association of selected VDR polymorphisms: Cdx2 (rs11658820), TaqI (rs7975232), BsmI (rs1544410), ApaI (rs7975232), and FokI (rs2228570) with the development of malocclusions. MATERIAL AND METHODS: A prospective observational study was performed. The examination consisted of a medical interview, intraand extraoral orthodontic diagnosis, alginate impression, cone beam computed tomography (CBCT), and venous blood sample to obtain genomic DNA and assess VDR polymorphisms. RESULTS: The rs11658820 polymorphism causes an almost 4-fold increase in the probability of the presence of a malocclusion. GT and TT genotypes of rs7975232 are also associated with a similar risk - almost 6 and almost 5 times higher, respectively. In turn, the effect of the rs2228570-AG and GG genotype polymorphisms on the occurrence of transversal anomalies was demonstrated (odds ratio (OR) = 8.46 and OR = 6.92, respectively). CONCLUSIONS: The association of individual polymorphisms with specific malocclusions should be carefully assessed, especially since some trends have been indicated.