Prostate cancer (PCa) is one of the most common oncological diseases in men. Some cases of PCa can be considered as clinical manifestations of hereditary cancer syndromes – diseases caused by germline mutations and characterized by an increased risk of developing certain types of tumors. The risk of PCa is increased in individuals with germline mutations in the BRCA1/2 genes and other homologous recombination repair genes (HRR), Lynch syndrome, Li-Fraumeni syndrome and a number of other hereditary diseases. We have described clinical and genetic characteristics, diagnostic methods, management and genetic counseling of patients with hereditary forms of PCa, as well as indications for targeted therapy. This review is aimed at clinical and laboratory geneticists, oncologists and related specialists.

The work highlights the variability of the mutational profile and clonal evolution of AML from diagnosis to relapse, with an emphasis on pediatric AML. The significance of molecular changes associated with age determines therapeutic approaches, which, in turn, influence the processes of relapse. Two main mechanisms of relapse are discussed: progression of the dominant allele of the driver mutation and evolution of clonal composition initiated by chemotherapy regimens. The contribution of epigenetic mechanisms in tumor progression as a way of forming chemoresistance and evolutionarily stable clones is assessed. As well as the role of aberrant methylation as an independent functional mechanism, taking into account the change in the mutational spectrum of a recurrent tumor.

PROS (PIK3CA-related overgrowth spectrum) is a heterogeneous group of diseases characterized by tissue overgrowth, vascular malformations, and other malformations. The cause of these pathologic conditions is a somatic activating PIK3CA mutation that occurs during embryogenesis. The wide phenotypic diversity of the disease complicates clinical diagnosis, so molecular genetic testing has a crucial role in the diagnosis and the decision to prescribe the PI3Kα inhibitor alpelisib. In this study, among 80 patients with suspected PROS, a variant in PIK3CA was identified in 29 patients using high-throughput sequencing of a panel of cell growth regulator genes, their clinical and molecular genetic characterization is presented, and further prospects for the development of molecular genetic diagnosis of PROS are discussed.

Background. The preservation of reproductive health and the birth of healthy children in couples where both spouses are carriers of genetic disorders are pressing healthcare issues. Many couples planning a pregnancy are not always aware of the risks of having a child with a severe genetic disease

Aim: to analyze the awareness of prenatal prevention and predictive diagnosis of cystic fibrosis (CF) among parents of CF patients who are healthy carriers of pathogenic variants of the CFTR gene, as well as among healthcare professionals (doctors from various specialties dealing with CF).

Methods. An online survey was conducted with 108 parents of CF patients and 84 physicians.

Results. Both parents of CF patients and healthcare professionals considered that the physician who should first explain the nature of the genetic disease to parents is a geneticist (42.9% and 42.8%, respectively). This responsibility can also be assigned to the attending physician, according to 32.1% of healthcare professionals and 33.9% of parents. There is no consensus on the specialty of the physician who should consult the patient regarding prenatal diagnosis. 39.2% of respondents believed this should be a geneticist in a medical genetic center (MGC), 19.0% – an obstetrician-gynecologist, 17.8% – the child’s attending physician from the CF/pulmonology center, 7.1% – a district pediatrician, and 9.5% – a reproductive specialist. The birth of a sick child significantly impacted the desire to have more children: 35 parents (32.3%) expressed their decision to abstain from further childbearing. Parents informed all family members about the disease risks in 78.7% of cases, only their spouse in 13.9%, and no one in 7.4% of respondents. A total of 86.1% of parents believed genetic technologies are necessary for the birth of a healthy child, but only 42.5% were willing to use prenatal diagnosis themselves. Awareness of prenatal diagnosis options was present in 79.6% of respondents, with 41.6% knowing about three types of diagnosis, including genetic screening at the pregnancy planning stage, embryo screening, and genetic diagnosis during pregnancy. Most surveyed parents received this information from the press/internet (29.6%) or from a physician at the MGC (28.7%).

Conclusion. The survey revealed a low level of awareness among both parents and healthcare professionals regarding prenatal diagnosis of CF.

Mutational changes in the STRC gene cause an autosomal recessive form of hearing loss (HL) type 16 (DFNB16, OMIM 603720), which in most cases is characterized by non-progressive, mild or moderate HL. One of the troubles of the testing STRC gene variants is the presence of the STRCP1 pseudogene (99.6% identity). In this regard, to detect and confirm various types of STRC mutations, a combined approach is used, since no single method detects all types of mutations. In this work, on a sample of 124 GJB2-negative patients with HL in Yakutia, we used optimized method for identifying copy number variations (CNVs) in the STRC locus, which allows us to detect homozygous cases of extended deletions using standard PCR, followed by direct detection of amplified fragments in 8% polyacrylamide gel. Using this method, homozygous cases of large deletions were detected in three patients, accounting for 2.41% (3/124). The identified CNV cases were verified using allele-specific PCR with an assessment of the approximate boundaries of the deleted fragments, to determine which we developed a primer system covering the analyzed chromosomal region. As a result, it was established that in one patient the large deletion covered only a copy of the STRC gene, in another – a copy of two genes STRC and CATSPER2, and in the third patient copies of the CKMT1A gene and the STRCP1 pseudogene were deleted. Taking into account affected individuals carrying causative homozygous deletions in the STRC gene region, the contribution of DFNB16 among GJB2-negative patients in Yakutia is at least 1.6% (2/124). Thus, the optimized method for searching for homozygous large deletions using standard PCR and the developed primer system for assessing the boundaries of the identified CNVs can be used as primary or alternative first-line tests for screening/ verification of large deletions in the STRC locus.

Melanoma is a complex disease influenced by changes in multiple genes and metabolic pathways that continue to evolve throughout the disease. Research into the genetic and molecular characteristics of melanoma is important for the development of new treatment strategies. The purpose of our study was to evaluate the survival rate and mutational status of the BRAF and NRAS genes in tumor material from patients diagnosed with cutaneous melanoma. A total of 54 patients with a confirmed diagnosis of cutaneous melanoma were included in the study: 36% were men (n=15), and women were 64% (n=39). The average age at diagnosis was 56 years. DNA was isolated from sections of paraffin blocks (FFPE) using a commercial kit QIAamp DNA FFPE Tissue Kit (QIAGENE, Germany). Analysis of the V600E mutation of the BRAF gene was carried out by allele-specific real-time PCR.  Exons 2 and 3 in the NRAS gene were analyzed by classical PCR (C1000 Touch BioRad, USA) followed by direct Sanger sequencing (ABI Prism 3500, Applied Biosystems, USA). Statistical analysis of the data was carried out using the Statistica 7.0 program. BRAF mutations were detected in 42.6% (V600E mutation 37.1%, V600K 5.4%), and NRAS mutations in 14.8% (Q61K 7%). In the remaining cases (42.6%), no changes were detected in any of the genes analyzed. The mutation status was closely related to the anatomical location of the tumor, so in the group with mutations in the BRAF and NRAS genes (65.3% and 37.0%, respectively; p = 0.002) patients with cutaneous primary lesions of the head and neck were noted. Mitotic activity was more frequently detected in primary tumors from patients with NRAS mutations than in patients with BRAF mutations (p = 0.002).