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The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The last decade has seen a growing awareness of epigenetic disregulations associated with cancer and other diseases. In the future, the measurement of epigenetic changes may represent an ideal diagnostic tool and could also provide targets for new therapies. Clinicians predict that epigenetic tests will be incorporated into most cancer treatment strategies in the coming years for the early detection, prognosis, and prediction of therapeutic response. However, there is also recognition that current epigenetic clinical tests are based mainly on individual genes or small panels of genes which may not have sufficient statistical representation to provide accurate results given the heterogeneity in genetic and epigenetic alterations in tumor cells both within and between individual patients. However, a factor facilitating the introduction of epigenomic technologies is the declining cost of genomic sequencing. Also, the Human Epigenome Project (HEP) is a multinational science project, with the stated aim of identifying, cataloguing, and interpreting genome-wide DNA methylation patterns of all human genes in all major tissues. It is financed by government funds and private investment via a consortium of genetic research organizations including the Wellcome Trust Sanger Institute (UK), Epigenomics AG (Germany/US), and the Centre National de Génotypage (France). Eventually, a comprehensive epigenomic map will be obtained that should be valuable in predicting the risk for certain diseases including cancer, and suggesting risk-lowering lifestyle changes that could be made for individuals.
Neuroendocrine tumours
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Sairah R Khan, Kathryn L Wallitt, Adil Al-Nahhas, Tara D Barwick
Most NETs are sporadic but familial clustering is recognized and hereditary syndromes that predispose to NETs include multiple endocrine neoplasia type 1 (MEN1) syndrome, von Hippel–Lindau (VHL) syndrome, neurofibromatosis 1 (NF1), and tuberous sclerosis (4,6). Novel technologies to analyse genomic and epigenomic characteristics have led to better understanding and characterization of a specific epigenetic subtype of NET and may lead to a better patient stratification than the current ones.
Neurodevelopment and placental omics
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Despina D. Briana, Ariadne Malamitsi-Puchner
Epigenomics is the study of heritable but feasibly environmentally modifiable control of gene expression potential without DNA sequence changes (25). Changes that alter genome function include DNA methylation, histone methylation, acetylation and phosphorylation, and changes in small noncoding RNA expression (21). Placental methylation is quite distinct from somatic tissues; while globally decreased, methylation is higher at some regions (26). The placenta is also unique among normal tissues in the presence of “partially methylated domains,” a large sequence along the chromosomes that show distinctly lower methylation (27). Application of array- and sequencing-based technologies can identify differences between pathological and normal placentas, for example, early onset preeclampsia (PE) is associated with a unique methylation profile (27). More interestingly, the detection of more subtle changes may be associated with maternal exposures, such as maternal stress and diet (27).
Advancements of next generation sequencing in the field of Rheumatoid Arthritis
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Ankita Pati, Dattatreya Kar, Jyoti Ranjan Parida, Ananya Kuanar
Epigenetic control has been demonstrated to take place at certain levels like the covalent modification of the proteins associated with DNA (histones), the direct chemical alterations in the DNA and modifications in the accessibility of chromatin as well at the higher-order structures. Furthermore, the terminology Epigenomics indicates a genome-wide mould of DNA modifications and accessibility of chromatin. Such patterns of epigenetics are plastic at the time of inflammatory processes [38]. In this context epigenetic modulations are seen to be important in disease states as well as inflammation; thus, it is crucial to understand the changes in epigenetics that may lead to rheumatic diseases has made the study of chromatin landscape and histone modifications easier by an in-depth analysis of these areas. In this context, the analyses of accessibility of chromatin as well as histone modifications are at the near stage, despite the changes in epigenetics within the disease-causing genes that have been identified in RA [39].
Epigenetics in drug disposition & drug therapy: symposium report of the 24th North American meeting of the International Society for the Study of Xenobiotics (ISSX)
Published in Drug Metabolism Reviews, 2022
Benjamin J. Maldonato, Ana G. Vergara, Jaydeep Yadav, Sarah M. Glass, Erickson M. Paragas, Dongying Li, Philip Lazarus, Joseph L. McClay, Baitang Ning, Ann K. Daly, Laura E. Russell
The symposium offered detailed presentations about the current landscape for epigenetics in drug disposition and drug discovery, and there was an engaging question and answer session after the presentations. The consensus was that there is still much more to be discovered about epigenetics to continue to advance human health, but current research is paving the way for these insights. The fast-developing advancements in genomics and epigenomics research provide the groundwork necessary to improve current drug treatment, while also breaking ground for novel therapeutics for difficult-to-treat diseases such as rare diseases, cancer, cardiovascular, and neurological diseases (Nguyen 2019). Similar to how far genomics research has helped advance drug discovery in the past 20 years (Russell et al. 2021), we anticipate that in the coming 20 years, epigenetics will play a critical role in discovering next-generation therapeutics with improved efficacy and safety, and will provide the ability to harness novel targets.
DNA methylation in pulmonary fibrosis and lung cancer
Published in Expert Review of Respiratory Medicine, 2022
Juan Duan, Baiyun Zhong, Zhihua Fan, Hao Zhang, Mengmeng Xu, Xiangyu Zhang, Yan Y Sanders
Recently, digital PCR has emerged as a sensitive tool for detecting epigenetic changes and point mutations [68–70]. Technological advances and increased use of high-throughput epigenetic screening approaches allow the identification of relevant epigenomic biomarkers. DNA methylation is one of the most widely studied biomarkers in cancer. Methylated biomarkers associated with lung fibrosis and lung cancer are shown in Table 1. Among them, RASSF1A (RAS association domain family protein 1A) is a candidate tumor suppressor that has been extensively studied in many human tumors [28]. It is frequently inactivated by methylation of its promoter region. Through analysis of bronchoalveolar lavage fluid (BALF) and venous blood, a recent study found that the positive rate of RASSF1A aberrant methylation in BALF was higher in the lung cancer group than in the control group [28]. Another study found that RASSF1A methylation status combined with either the RARB or L1RE1 panel could achieve satisfactory sensitivity and specificity in lung cancer diagnosis, especially for separating lung cancer and non-cancerous tissue [71]. SOX17 is another proposed biomarker whose promoter has a significantly higher frequency of methylation in primary and advanced NSCLC tumors and in corresponding plasma samples [72]. Methylation of the SOX17 promoter also has a statistically significant effect on survival time [72].