Aliya Ramilevna Zaripova

For various types of solid tumors, bones are the most common location of metastases. Bone is a dynamic organ capable of simultaneously performing multiple auxiliary functions in the body. Osteoblasts and osteoclasts and their changes play a significant role in bone remodeling. Aim. To summarize current data on bone metastases for better understanding of biological nature of oncogenesis. The article analyzes recent scientific publications containing information on molecular mechanisms of metastasis into the bone from the National Center for Biotechnology Information (NCBI), eLibrary and Google Scholar databases, as well as characterizes bone cells and their role in oncogenesis. Knowledge and deep understanding of bone metastasis in various solid tumors are necessary for development of accurate diagnostic methods and effective modern treatment of patients with bone metastases. Currently, the mechanisms of cancer metastasis and interactions between metastatic cancer cells and bone microenvironment are not completely understood. Epigenetic changes associated with differentiation of osteoblasts and osteoclasts and cell signal transduction play a large role in bone remodeling in various malignant neoplasms. Increased bone resorption is caused by disbalance between osteoblasts and osteoclasts. Osteoclast activity leads to release of growth factors from the bone matrix necessary for tumor cell multiplication in the bone.

Background. Bladder cancer (BC) is one of the most common cancers worldwide, representing an urgent problem of modern oncology. Various external and internal environmental factors increase the disease risk. Genetic susceptibility to BC is unquestioned and actively researched nowadays. Aim. To analyze current advances in genetic factors of BC and to assess the prospects for further research in this area. Materials and methods. A systematic analysis of modern literature available in the PubMed database was conducted. Results and conclusion. A small part of BC cases is associated with hereditary syndromes, which are characterized by BC development. Genes regulating cellular metabolism, DNA repair, and cell cycle are associated with BC. Today, there is a clear understanding that high-risk genes are rarely involved in the development of most BC cases, but there are many polymorphic loci with low penetrance and moderate effects that acting together increase BC risk, indicating a complex polygenic inheritance pattern for this disease.

Background. Pancreatic cancer (PC) is an aggressive malignancy with a high mortality rate. Pancreatic ductal adenocarcinoma constitutes approximately 90 % of pancreatic cancers, and is frequently diagnosed at an advanced stage. The disease is distinguished by the presence of tumor micrometastasis prior to the onset of clinical symptoms, as well as rapid progression. There are currently no effective screening methods for the disease.Aim of the study: analysis of available literature data about susceptibility genes and molecular mechanisms of PC.Material and methods. The search for relevant sources was performed in the PubMed (NCBI), Elibrary, GoogleScholar, publications from January 2000 to December 2024 were included. Of the 959 papers analyzed, 60 were used to write the review, 27 of which were published in the last five years.Results. Approximately 10 % of pancreatic adenocarcinoma patients are carriers of germinal pathogenic variants that cause an increased risk of PC. These variants predominantly occur in DNA damage repair genes. Tumor cells undergo complex multistep genetic alterations, and the accumulation of these changes facilitates the activation of various oncogenes that contribute to the progression of PC. Research in the field of molecular genetics makes it possible to identify groups of patients with certain genetic alterations who need to be prescribed targeted drugs.Conclusion. This article provides an overview of current understanding of the genetic predisposition to PC. The functional/clinical significance of proteins involved in the pathogenesis of the disease was described. Genetic alterations of PC were discussed.

Osteogenesis imperfecta (OI) is a heterogeneous group of genetic diseases characterized by bone fragility and low bone mass. We report the identification of two unrelated families with OI of Bashkir origin—one with homozygous, the other with compound heterozygous probably pathogenic variants of the P3H1 gene, as well as one case of heterozygous carriage in a patient with clinical manifestations that do not correspond in severity to type VIII OI. Thus, an ethnospecific previously undescribed population aspect of the prevalence of recessive pathogenic variants p.Glu351Ter, p.Gly650Arg, 1720 + 4G>A in the P3H1 gene associated with various clinical phenotypes has been identified.

Background/Objectives: Cervical cancer (CC) remains a significant global health challenge, characterized by genetic heterogeneity and a complex molecular landscape, both of which contribute to its pathogenesis. This study aimed to investigate germline variants in proto-oncogenes and tumor suppressor genes in cervical cancer patients, with the objective of clarifying their potential role in disease development. Methods: We utilized a custom next-generation sequencing (NGS) panel targeting 48 genes implicated in oncogenesis. Germline DNA samples from cervical cancer patients were analyzed in order to identify nucleotide sequence alterations. Variants were classified according to pathogenicity and clinical relevance, based on established guidelines. Results: A total of 148 nucleotide variants were detected within the cohort. Of these, 35 variants (23.6%) were classified as benign. In contrast, 105 variants (70.9%) were identified as variants of uncertain significance (VUSs). Moreover, seven pathogenic or likely pathogenic mutations were discovered, along with the polymorphic variant rs1042522 in the TP53 gene, which has been associated with an increased risk of cervical cancer. Conclusions: Our findings contribute to expanding our understanding of the molecular genetic landscape of cervical cancer. They emphasize the potential contribution of rare germline mutations to its development and progression. These results highlight the importance of comprehensive genetic screening in order to improve diagnostic and therapeutic approaches for cervical cancer patients.

Cervical cancer (CC) remains a significant global health challenge, characterized by its genetic heterogeneity and complex molecular landscape. The current study investigates the germline variants in proto-oncogenes and tumor suppressor genes among patients diagnosed with cervical cancer. Utilizing a custom NGS panel targeting 48 genes implicated in oncogenesis, we identified 148 nucleotide sequence alterations across the cohort. Of these, 35 variants (23.6%) were classified as benign, while 105 (70.9%) were categorized as variants of uncertain significance (VUS), whose clinical relevance remains to be elucidated. Moreover, we discovered seven pathogenic or likely pathogenic mutations, as well as a polymorphic variant rs1042522 in the TP53 gene, which has been previously associated with an increased risk of CC. Our findings contribute to the understanding of the molecular-genetic landscape of cervical cancer, highlighting the potential impact of rare germline mutations on the disease's pathogenesis and progression. This study underscores the importance of comprehensive genetic screening in improving the diagnostic and therapeutic strategies for cervical cancer patients.

Osteogenesis imperfecta (OI) is a large group of genetically heterogeneous diseases resulting from decreased bone density and an abnormal microarchitecture, which are clinically manifested by abnormal bone fractures. A distinctive clinical feature of this group of diseases is the presence of spontaneous fractures and skeletal deformities. However, the clinical manifestations of different types of OI are characterized by marked polymorphism with variable severity of skeletal and extra-skeletal features. Previous studies have shown that a mutation (c.-14C>T) in the IFITM5 gene is responsible for autosomal dominant OI type V. However, the mutation has a variable expression pattern and marked clinical heterogeneity. In this study, a clinical and genetic analysis of 12 cases with molecularly confirmed OI type V from 12 unrelated families was performed. Significant clinical heterogeneity of the disease with the same molecular defect was detected. In six subjects (50%), there were no classic signs of OI type V (formation of a hyperplastic bone callus, calcification of the interosseous membrane and dislocation of the radial head). In all cases, the mutation occurred de novo.

Osteogenesis imperfecta (OI) is an inherited disease of bone characterized by increased bone fragility. Here, we report the results of the molecular architecture of osteogenesis imperfecta research in patients from Bashkortostan Republic, Russia. In total, 16 mutations in COL1A1, 11 mutations in COL1A2, and 1 mutation in P3H1 and IFIMT5 genes were found in isolated states; 11 of them were not previously reported in literature. We found mutations in CLCN7, ALOX12B, PLEKHM1, ERCC4, ARSB, PTH1R, and TGFB1 that were not associated with OI pathogenesis in patients with increased bone fragility. Additionally, we found combined mutations (c.2869C>T, p. Gln957* in COL1A1 and c.1197+5G>A in COL1A2; c.579delT, p. Gly194fs in COL1A1 and c.1197+5G>A in COL1A2; c.2971G>C, p. Gly991Arg in COL1A2 and c.212G>C, p.Ser71Thr in FGF23; c.-14C>T in IFITM5 and c.1903C>T, p. Arg635* in LAMB3) in 4 patients with typical OI clinic phenotypes.

Osteogenesis imperfecta (imperfect osteogenesis in the Russian literature) is the most common hereditary form of bone fragility, it is a genetically and clinically heterogeneous disease with a wide range of clinical severity, often leading to disability from early childhood. It is based on genetic disorders leading to a violation of the structure of bone tissue, which leads to frequent fractures, impaired growth and posture, with the development of characteristic disabling bone deformities and associated problems, including respiratory, neurological, cardiac, renal impairment, hearing loss. Osteogenesis imperfecta occurs in both men and women, the disease is inherited in both autosomal dominant and autosomal recessive types, there are sporadic cases of the disease due to de novomutations, as well as X-linked forms. The term “osteogenesis imperfecta” was coined by W. Vrolick in the 1840s. The first classification of the disease was made in 1979 and has been repeatedly reviewed due to the identification of the molecular cause of the disease and the discovery of new mechanisms for the development of osteogenesis imperfecta. In the early 1980s, mutations in two genes of collagen type I (COL1A1and COL1A2) were first associated with an autosomal dominant inheritance type of osteogenesis imperfecta. Since then, 18 more genes have been identified whose products are involved in the formation and mineralization of bone tissue. The degree of genetic heterogeneity of the disease has not yet been determined, researchers continue to identify new genes involved in its pathogenesis, the number of which has reached 20. In the last decade, it has become known that autosomal recessive, autosomal dominant and X-linked mutations in a wide range of genes, encoding proteins that are involved in the synthesis of type I collagen, its processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells, cause imperfect osteogenesis. A large number of causative genes complicated the classical classification of the disease and, due to new advances in the molecular basis of the disease, the classification of the disease is constantly being improved. In this review, we systematized and summarized information on the results of studies in the field of clinical and genetic aspects of osteogenesis imperfecta and reflected the current state of the classification criteria for diagnosing the disease.