Epigenetics and diagnostic

Bromine domain protein 2 (BRD2), a member of the Bromodomain and extraterminal domain (BET) protein family, is a crucial epigenetic regulator with significant function in various diseases and cellular processes. The central function of BRD2 is modulating gene transcription by binding to acetylated lysine residues on histones and transcription factors. This review highlights key findings on BRD2 in recent years, emphasizing its roles in maintaining genomic stability, influencing chromatin spatial organization, and participating in transcriptional regulation...

BACKGROUND: Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. RESULTS: We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma...

Genomic biotechnologies have seen rapid development over the past two decades, allowing for both the inference and modification of genetic and epigenetic information at the single cell level. While these tools present enormous potential for basic research, diagnostics, and treatment, they also raise difficult issues of how to design research studies to deploy these tools most effectively. In designing a study at the population or individual level, a researcher might combine several different sequencing modalities and sampling protocols, each with different utility, costs, and other tradeoffs...

HLA-G expression of tumors and upon viral infections is involved in their immune escape leading to the evasion from both T and NK cell recognition. The underlying mechanisms of HLA-G expression in both pathophysiologic conditions are broad and range from genetic abnormalities to epigenetic, transcriptional and posttranscriptional regulation. This review summarizes the current knowledge of the frequency, regulation and clinical relevance of HLA-G expression upon neoplastic and viral transformation, its interaction with components of the microenvironment as well as its potential as diagnostic marker and/or therapeutic target...

The development of epigenetic clocks, or the DNA methylation-based inference of age, is an emerging tool for ageing in free ranging populations. In this study, we developed epigenetic clocks for three species of large mammals that are the focus of extensive management throughout their range in North America: white-tailed deer, black bear and mountain goat. We quantified differential DNA methylation patterns at over 30,000 cytosine-guanine sites (CpGs) from tissue samples of all three species (black bear n = 49; white-tailed deer n = 47; mountain goat n = 45)...

Telomerase reverse transcriptase (TERT) promoter mutation is associated with an aggressive clinical course in thyroid carcinomas. Therefore, detection of TERT promoter mutation is essential for proper patient management. 5-Hydroxymethylcytosine (5hmC) is an epigenetic marker involved in the DNA demethylation pathway, and its loss has been observed in various tumors. Loss of 5hmC has also been reported in thyroid carcinomas and is presented as a possible predictive biomarker for TERT promoter mutation and worse prognosis...

One of the challenges of modern-day living is to resist the temptation of overfeeding and sedentariness and maintain a healthy body and mind. On a favorable genetic and epigenetic background, a high-fat diet combined with lack of physical exercise constitutes the foundation for severe metabolic disturbances including steatotic liver disease. In our case-control study, we had the aim of establishing the role of selected micro-RNAs-miR-122, miR-192, miR-33a, and miR-33b-as superior biomarkers for the diagnosis and prognosis of steatotic liver in a 36-patient cohort compared to 12 healthy controls...

Colorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different characteristics in immunotherapy. Low sensitivity of diagnostic biomarkers and metastasis are still the principal cause of mortality, especially in MSI. Here, applying computational programs, we identified recurring expression programs based on single cell RNA sequencing (scRNA-Seq) data of CRC cell lines...

DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single-base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance...

An increasing body of research has demonstrated the significant role of long non-coding RNAs (lncRNAs) in the pathogenesis of stroke. They can actively contribute to the disease's progression either by directly participating in its pathogenesis or by acting as mediators through competing endogenous RNA (ceRNA) mechanisms. Concurrently, epigenetics plays a pivotal role in the pathological mechanisms underlying stroke. Epigenetic factors serve as valuable markers for disease progression, diagnostic biomarkers, and novel therapeutic targets...

Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis...

Colorectal cancer (CRC), a prevalent malignant tumor of the digestive system, ranks as the third and second in global incidence and mortality, respectively, in 2020, with 1.93 million new cases (≈10% of all cancers). There are 940,000 deaths (≈9.4% of all cancers), and the incidence of CRC in younger patients (under 50 years of age) has become a new trend. The pathogenesis of CRC is primarily attributed to a series of genetic and epigenetic abnormalities within normal colonic epithelial cells, coupled with the reshaping of the tumor microenvironment in the surrounding stroma...

The advent of CRISPR/Cas9 technology has revolutionized genome editing, enabling the attainment of once-unimaginable goals. CRISPR/Cas's groundbreaking attributes lie in its simplicity, versatility, universality, and independence from customized DNA-protein systems, erasing the need for specialized expertise and broadening its scope of applications. It is therefore more and more used for genome modification including the generation of mutants. Beyond such editing scopes, the recent development of novel or modified Cas-based systems has spawned an array of additional biotechnological tools, empowering both fundamental and applied research...

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD...

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features. METHODS: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS)...

Systemic sclerosis is a complex idiopathic disease originating from an intricate interplay between genetic susceptibility, environmental factors, and epigenetic modifications. This scoping review aims to map the advancements made regarding DNA methylation abnormalities and histone modifications in systemic sclerosis in the past decade. A literature search was conducted using three electronic databases (Scopus, Web of Science and PubMed) to identify relevant articles. A total of 44 studies were selected for this review, demonstrating the critical contribution of epigenetic perturbations in multiple cell types to disease pathogenesis...

In pancreatic ductal adenocarcinoma (PDAC), no recurrent metastasis-specific mutation has been found, suggesting that epigenetic mechanisms, such as DNA methylation, are the major contributors of late-stage disease progression. Here, we performed the first whole-genome bisulfite sequencing (WGBS) on mouse and human PDAC organoid models to identify stage-specific and molecular subtype-specific DNA methylation signatures. With this approach, we identified thousands of differentially methylated regions (DMRs) that can distinguish between the stages and molecular subtypes of PDAC...

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) poses a significant threat to the quality of life for people worldwide. Regrettably, effective treatment strategies for this disease remain elusive in clinical practice due to the unclear understanding of its molecular mechanisms. Therefore, this study was devised to address these issues and identify novel diagnostic, therapeutic, and prognostic biomarkers for DLBCL. METHODS: Gene expression and clinical data for DLBCL patients were retrieved from The Cancer Genome Atlas (TCGA) database, and relevant clinical data, tumor mutational burden (TMB), and gene expression levels were extracted...

Mammalian females are born with a finite number of follicles in their ovaries that is referred to as the ovarian reserve. There is a large amount of variation between females in the number of antral follicles that they are born with, but this number is positively correlated to size of the ovarian reserve, has a strong repeatability within a female, and a moderate heritability. Although the heritability is moderate, numerous external factors including health, nutrition, ambient temperature, and litter size influence the size and function of the ovarian reserve throughout life...

BACKGROUND: The unknown tissue of origin in head and neck cancer of unknown primary (hnCUP) leads to invasive diagnostic procedures and unspecific and potentially inefficient treatment options for patients. The most common histologic subtype, squamous cell carcinoma, can stem from various tumor primary sites, including the oral cavity, oropharynx, larynx, head and neck skin, lungs, and esophagus. DNA methylation profiles are highly tissue-specific and have been successfully used to classify tissue origin...