Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world’s population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic and environmental factors. An increasing body of evidence pinpoints that epigenetic modifications play an important role in the regulation of RA pathogenesis. Epigenetics causes heritable phenotype changes that are not determined by changes in the DNA sequence. The major epigenetic mechanisms include DNA methylation, histone proteins modifications and changes in gene expression caused by microRNAs and other non-coding RNAs. These modifications are reversible and could be modulated by diet, drugs, and other environmental factors. Specific changes in DNA methylation, histone modifications and abnormal expression of non-coding RNAs associated with RA have already been identified. This review focuses on the role of these multiple epigenetic factors in the pathogenesis and progression of the disease, not only in synovial fibroblasts, immune cells, but also in the peripheral blood of patients with RA, which clearly shows their high diagnostic potential and promising targets for therapy in the future.

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.

Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel. Mutations were detected most frequently in the CDH1 (13/47) and TP53 (12/47) genes. As expected, somatic CDH1 mutations were positively correlated with distant metastases (p = 0.019) and tumours with signet ring cells (p = 0.043). These findings confirm the association of the CDH1 mutations with diffuse GC type. TP53 mutations were found to be significantly associated with a decrease in overall survival in patients with Lauren diffuse-type tumours (p = 0.0085), T3-T4 tumours (p = 0.037), and stage III-IV tumours (p = 0.013). Our results confirm that the detection of mutations in the main driver genes may have a significant prognostic value for GC patients and provide an independent GC-related set of clinical and molecular genetic data.Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide after lung cancer and breast cancer. The incidence of GC is particularly high in East Asia, including China, Japan and Korea, and in South America 1 . Based on the Lauren classification, GC is divided into two main types, namely, intestinal and diffuse, which have different epidemiological, morphological and clinical features. Intestinal GC commonly appears in elderly patients with multifocal atrophic gastritis, which is accompanied by intestinal metaplasia or dysplasia. Diffuse GC is more common in younger patients, and its association with atrophic gastritis or intestinal metaplasia is not obvious. Clinical differences between these two types reflect different mechanisms of the development and molecular pathogenesis of tumours 2 . However, Lauren's classification is not closely associated with treatment and prognosis, necessitating the development of a classification combining clinical, morphological, and molecular features of GC in response to certain therapeutic modalities.Comprehensive studies, including analyses of the genome, epigenome, proteome and transcriptome, offered an entirely different view on the tumour, moving it out of a single plane and into a multidimensional spatial image. The ability to determine the tumour-specific spectrum of genetic and epigenetic changes enables us to expand our understanding of the molecular pathogenesis of the tumour and to obtain information about the potential of targeted therapies. Mutational profiling is one way to classify tumours depending on the mutation spectrum into specific molecular subtypes that differ from the standard morphological classification. The results of recent studies, such as TCGA Validation of mutations detected by next-generation sequencing. Validation of th...

No abstract