Cancer AND epigenom

Inferring the cancer-type specificities of ultra-rare, genome-wide somatic mutations is an open problem. Traditional statistical methods cannot handle such data due to their ultra-high dimensionality and extreme data sparsity. To harness information in rare mutations, we have recently proposed a formal multilevel multilogistic "hidden genome" model. Through its hierarchical layers, the model condenses information in ultra-rare mutations through meta-features embodying mutation contexts to characterize cancer types...

Chronic lymphocytic leukemia, in spite of recent advancements, is still an incurable disease; the majority of patients eventually acquire resistance to treatment through relapses. In all subtypes of chronic lymphocytic leukemia, the disruption of normal B-cell homeostasis is thought to be mostly caused by the absence of apoptosis. Consequently, apoptosis induction is crucial to the management of this illness. Damaged biological components can accumulate as a result of the oxidation of intracellular lipids, proteins, and DNA by reactive oxygen species...

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods...

Although cancer initiation and progression are generally associated with the accumulation of somatic mutations1,2 , substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility3-6 , suggesting that genetic mechanisms might not be the only drivers of malignant transformation7 . However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila...

Gut microbiota interacts with host epithelial cells and regulates many physiological functions such as genetics, epigenetics, metabolism of nutrients, and immune functions. Dietary factors may also be involved in the etiology of colorectal cancer (CRC), especially when an unhealthy diet is consumed with excess calorie intake and bad practices like smoking or consuming a great deal of alcohol. Bacteria including Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli ( E. coli ) actively participate in the carcinogenesis of CRC...

PURPOSE OF REVIEW: Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation is a central feature of GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between GIM, local and systemic inflammation, and the microbiome and its metabolites, and explores recent research on therapeutics that target this relationship. RECENT FINDINGS: Recent literature underscores the pivotal role of inflammation in GIM, elucidating its bidirectional relation with disturbance of the gut microbiota composition and intestinal permeability...

The effects of PM2.5 on human health fluctuate greatly among various age groups, influenced by a range of physiological and immunological reactions. This paper compares the pathogenesis of the disease caused by PM2.5 in people of different ages, focusing on how children, adults, and the elderly are each susceptible to it because of differences in their bodies. Regarding children, exposure to PM2.5 is linked to many negative consequences. These factors consist of inflammation, oxidative stress, and respiratory problems, which might worsen pre-existing conditions and potentially cause neurotoxicity and developmental issues...

BACKGROUND: Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with Helicobacter pylori is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia...

Cervical cancer (CC) remains one of the most common malignancies among women worldwide, posing a serious threat to women's health. N6-methyladenosine (m6 A) modification, as the most abundant type of RNA methylation modification, and has been found to play a crucial role in various cancers. Current research suggests a close association between RNA m6 A modification and the occurrence and progression of CC, encompassing disruptions in m6 A levels and its regulatory machinery. This review summarizes the current status of m6 A modification research in CC, explores the mechanisms underlying m6 A levels and regulators (methyltransferases, demethylases, reader proteins) in CC and examines the application of small-molecule inhibitors of m6 A regulators in disease treatment...

Triple-negative breast cancer (TNBC) has negative expressions of ER, PR and HER2. Due to the insensitivity to both endocrine therapy and HER2-targeted therapy, the main treatment method for TNBC is cytotoxic chemotherapy. However, the curative effect of chemotherapy is limited because of the existence of acquired or intrinsic multidrug resistance. MicroRNAs (miRNAs) are frequently dysregulated in malignant tumors and involved in tumor occurrence and progression. Interestingly, growing studies show that miRNAs are involved in chemoresistance in TNBC...

Epigenetic mechanisms control and regulate normal chromatin structure and gene expression patterns, with epigenetic dysregulation observed in many different cancer types. Importantly, epigenetic modifications are reversible, offering the potential to silence oncogenes and reactivate tumor suppressors. Small molecule drugs manipulating these epigenetic mechanisms are at the leading edge of new therapeutic options for cancer treatment. The clinical use of histone deacetyltransferases inhibitors (HDACi) demonstrates the effectiveness of targeting epigenetic mechanisms for cancer treatment...

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Triple-negative breast cancer (TNBC) is a unique breast cancer subtype characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Since TNBC lacks ER, PR, and HER2, there are currently no drugs that specifically target TNBC. Therefore, the development of new drugs or effective treatment strategies to target TNBC has become an urgent clinical need. Research has shown that the application of histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors leads to genomic and epigenomic instability...

Cigarette smoke changes the genomic and epigenomic imprint of cells. In this study, we investigated the biological consequences of extended cigarette smoke exposure on dental pulp stem cells (DPSCs) and the potential roles of miRNAs. DPSCs were treated with various doses of cigarette smoke condensate (CSC) for up to six weeks. Cell proliferation, survival, migration, and differentiation were evaluated. Cytokine and miRNA expression were profiled. The results showed that extended exposure to CSC significantly impaired the regenerative capacity of the DPSCs...

BACKGROUND: This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. METHODS: Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations...

Covering: 1970 through June of 2023Verticillins are epipolythiodioxopiperazine (ETP) alkaloids, many of which possess potent, nanomolar-level cytotoxicity against a variety of cancer cell lines. Over the last decade, their in vivo activity and mode of action have been explored in detail. Notably, recent studies have indicated that these compounds may be selective inhibitors of histone methyltransferases (HMTases) that alter the epigenome and modify targets that play a crucial role in apoptosis, altering immune cell recognition, and generating reactive oxygen species...

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues 1,2 . Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B) 3-6 . However, how APOBEC3A/B enzymes shape the tumor evolution in the presence of exogenous mutagenic processes is largely unknown. Here, by combining deep whole-genome sequencing with multi-omics profiling of 309 lung cancers from smokers with detailed tobacco smoking information, we identify two subtypes defined by low ( LAS ) and high ( HAS ) APOBEC mutagenesis...

Chromatin undergoes dynamic regulation through reversible histone post-translational modifications (PTMs), orchestrated by "writers," "erasers," and "readers" enzymes. Dysregulation of these histone modulators is well implicated in shaping the cancer epigenome and providing avenues for precision therapies. The approval of six drugs for cancer therapy targeting histone modulators, along with the ongoing clinical trials of numerous candidates, represents a significant advancement in the field of precision medicine...

Precision oncology is based on deep knowledge of the molecular profile of tumors, allowing for more accurate and personalized therapy for specific groups of patients who are different in disease susceptibility as well as treatment response. Thus, onco-breastomics is able to discover novel biomarkers that have been found to have racial and ethnic differences, among other types of disparities such as chronological or biological age-, sex/gender- or environmental-related ones. Usually, evidence suggests that breast cancer (BC) disparities are due to ethnicity, aging rate, socioeconomic position, environmental or chemical exposures, psycho-social stressors, comorbidities, Western lifestyle, poverty and rurality, or organizational and health care system factors or access...

Topic modeling is a popular technique in machine learning and natural language processing, where a corpus of text documents is classified into themes or topics using word frequency analysis. This approach has proven successful in various biological data analysis applications, such as predicting cancer subtypes with high accuracy and identifying genes, enhancers, and stable cell types simultaneously from sparse single-cell epigenomics data. The advantage of using a topic model is that it not only serves as a clustering algorithm, but it can also explain clustering results by providing word probability distributions over topics...