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Personalized epigenetics

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https://www.readbyqxmd.com/read/28523552/epigenetics-of-huntington-s-disease
#1
Silvia Bassi, Takshashila Tripathi, Alan Monziani, Francesca Di Leva, Marta Biagioli
Huntington's disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957-961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971-983, 1993). The expanded CAG repeat, translated into a lengthened glutamine tract at the amino terminus of the huntingtin protein, affects its structural properties and functional activities...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#2
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28511181/1-cmdb-a-curated-database-of-genomic-variations-of-the-one-carbon-metabolism-pathway
#3
Manoj K Bhat, Veerendra P Gadekar, Aditya Jain, Bobby Paul, Padmalatha S Rai, Kapaettu Satyamoorthy
BACKGROUND: The one-carbon metabolism pathway is vital in maintaining tissue homeostasis by driving the critical reactions of folate and methionine cycles. A myriad of genetic and epigenetic events mark the rate of reactions in a tissue-specific manner. Integration of these to predict and provide personalized health management requires robust computational tools that can process multiomics data. The DNA sequences that may determine the chain of biological events and the endpoint reactions within one-carbon metabolism genes remain to be comprehensively recorded...
May 17, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28490462/genome-wide-dna-methylation-analysis-reveals-gabbr2-as-a-novel-epigenetic-target-for-egfr-19-deletion-lung-adenocarcinoma-with-induction-erlotinib-treatment
#4
Xiaomin Niu, Fatao Liu, Yi Zhou, Zhen Zhou, Daizhan Zhou, Ting Wang, Ziming Li, Xiangyun Ye, Yongfeng Yu, Xiaoling Weng, Hong Zhang, Junyi Ye, Meilin Liao, Yun Liu, Zhiwei Chen, Shun Lu
Purpose: The last decade has witnessed the rapid development of personalized targeted therapies in lung cancer. It is still unclear whether epigenetic changes are involved in the response to tyrosine kinase inhibitor (TKI) treatment in epidermal growth factor receptor (EGFR) mutated lung cancer. <p>Experimental Design: Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the methylation changes in paired tissues before and after erlotinib treatment for 42 days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients (N=2) with EGFR 19 deletion...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28484264/the-role-of-lnk-sh2b3-genetic-alterations-in-myeloproliferative-neoplasms-and-other-hematological-disorders
#5
REVIEW
N Maslah, B Cassinat, E Verger, J-J Kiladjian, L Velazquez
Malignant hematological diseases are mainly due to the occurrence of molecular abnormalities leading to the deregulation of signaling pathways essential for precise cell behavior. High resolution genome analysis using microarray and large-scale sequencing have helped identify several important acquired gene mutations that are responsible for such signaling deregulations across different hematological malignancies. In particular, the genetic landscape of classical myeloproliferative neoplasms (MPNs) has been in large part completed with the identification of driver mutations (targeting the cytokine receptor/JAK2 pathway) that determine MPN phenotype, as well as additional mutations mainly affecting the regulation of gene expression (epigenetics or splicing regulators) and signaling...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28481734/hlj1-dnajb4-gene-is-a-novel-biomarker-candidate-in-breast-cancer
#6
Tolga Acun, Natalie Doberstein, Jens K Habermann, Timo Gemoll, Christoph Thorns, Emin Oztas, Thomas Ried
Breast cancer is the most common cancer type and cause of cancer-related mortality among women worldwide. New biomarker discovery is crucial for diagnostic innovation and personalized medicine in breast cancer. Heat shock proteins (HSPs) have been increasingly reported as biomarkers and potential drug targets for cancers. HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers. However, the role of the HLJ1 gene in breast cancer is currently unknown...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28472521/the-value-of-biosamples-in-smoking-cessation-trials-a-review-of-genetic-metabolomic-and-epigenetic-findings
#7
Nancy L Saccone, James W Baurley, Andrew W Bergen, Sean P David, Hannah R Elliott, Marilyn G Foreman, Jaakko Kaprio, Thomas M Piasecki, Caroline L Relton, Laurie Zawertailo, Laura J Bierut, Rachel F Tyndale, Li-Shiun Chen
Evidence is emerging that certain genotypes and biomarkers are associated with smoking cessation success and efficacy of smoking cessation treatments. We review key findings that open potential avenues for personalizing smoking cessation treatment according to an individual's genetic or metabolic profile. These results provide important incentive for smoking cessation researchers to collect biosamples and perform genotyping in research studies and clinical trials.
May 3, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28471941/basic-science-and-pathogenesis-of-ageing-with-hiv-potential-mechanisms-and-biomarkers
#8
Claire Lagathu, Andrea Cossarizza, Véronique Béréziat, Milena Nasi, Jacqueline Capeau, Marcello Pinti
: The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28441730/regulatory-mirnas-in-colorectal-carcinogenesis-and-metastasis
#9
REVIEW
Yongchen Guo, Yonghua Bao, Wancai Yang
Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in carcinogenesis and progression through regulating of oncogenic signaling pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-β, and inflammatory signaling pathways, stemness, and epithelial-mesenchymal transition, for carcinogenesis and metastasis in colorectal cancer...
April 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28415743/survival-differences-of-cimp-subtypes-integrated-with-cna-information-in-human-breast-cancer
#10
Huihan Wang, Weili Yan, Shumei Zhang, Yue Gu, Yihan Wang, Yanjun Wei, Hongbo Liu, Fang Wang, Qiong Wu, Yan Zhang
CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy number and methylation status evaluation...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410846/initiative-for-molecular-profiling-and-advanced-cancer-therapy-and-challenges-in-the-implementation-of-precision-medicine
#11
Apostolia-Maria Tsimberidou
In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center...
February 10, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28397399/belinostat-exerts-anti-tumor-cytotoxicity-through-the-ubiquitin-proteasome-pathway-in-lung-squamous-cell-carcinoma
#12
Li Ren Kong, Tuan Zea Tan, Weijie Richard Ong, Chonglei Bi, Hung Huynh, Soo Chin Lee, Wee Joo Chng, Pieter Johan Adam Eichhorn, Boon Cher Goh
There have been advances in personalized therapy directed by molecular profiles in lung adenocarcinoma but not in lung squamous cell carcinoma (SCC). The lack of actionable driver oncogenes in SCC has restricted the use of small molecule inhibitors. Here, we show that SCC cell lines displayed differential sensitivities to belinostat, a pan-histone deacetylase (HDAC) inhibitor. Phosphoproteomic analysis of belinostat-treated SCC cells revealed significant downregulation of the MAPK pathway, along with induction of apoptosis...
April 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28395317/indoor-air-quality-in-photocopy-centers-nanoparticle-exposures-at-photocopy-workstations-and-the-need-for-exposure-controls
#13
John Martin, Philip Demokritou, Susan Woskie, Dhimiter Bello
Background: Photocopiers emit large amounts of nanoparticles (NP) and are a significant source of indoor air pollution. These emissions induce airway inflammation, irritation, and systemic oxidative stress in humans, lung injury and inflammation in animals, and cytotoxicity and epigenetic modifications in vitro. However, little is known regarding NP exposures at the workstation in the photocopy work environment, or the extent and use of emission controls. Objective: To survey the photocopy work environment with regards to emissions controls and to evaluate IAQ with emphasis on NP exposure at the operator's workstation...
January 1, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/28388695/regulation-of-drug-metabolism-and-toxicity-by-multiple-factors-of-genetics-epigenetics-lncrnas-gut-microbiota-and-diseases-a-meeting-report-of-the-21-st-international-symposium-on-microsomes-and-drug-oxidations-mdo
#14
Ai-Ming Yu, Magnus Ingelman-Sundberg, Nathan J Cherrington, Lauren M Aleksunes, Ulrich M Zanger, Wen Xie, Hyunyoung Jeong, Edward M Morgan, Peter J Turnbaugh, Curtis D Klaassen, Aadra P Bhatt, Matthew R Redinbo, Pengying Hao, David J Waxman, Li Wang, Xiao-Bo Zhong
Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21(st) International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28378229/advances-in-the-development-of-molecularly-targeted-agents-in-non-small-cell-lung-cancer
#15
Saoirse O Dolly, Dearbhaile C Collins, Raghav Sundar, Sanjay Popat, Timothy A Yap
Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival...
May 2017: Drugs
https://www.readbyqxmd.com/read/28377395/integrated-approach-of-nutritional-and-molecular-epidemiology-mineralogical-and-chemical-pollutant-characterisation-the-protocol-of-a-cross-sectional-study-in-women
#16
Martina Barchitta, Annalisa Quattrocchi, Andrea Maugeri, Germana Barone, Paolo Mazzoleni, Alfio Catalfo, Guido De Guidi, Maria Iemmolo, Nunzio Crimi, Antonella Agodi
INTRODUCTION: Environmentally-related health and disease are the result of the exposome, the totality of a person's environmental exposures, from all sources and routes, across their lifespan. Epigenetic phenomena, including DNA methylation, can be potentially modified by environmental and lifestyle factors, and result in environmental reprogramming of the genome for exposed individuals and for future generations of offspring. OBJECTIVE: The objective of the project is to evaluate the risk of DNA hypomethylation due to air pollution, Mediterranean diet adherence, folate intake, and demographic and socioeconomic factors, in healthy women living in the metropolitan area of Catania, Italy...
April 4, 2017: BMJ Open
https://www.readbyqxmd.com/read/28367231/molecular-subtyping-of-pancreatic-cancer-translating-genomics-and-transcriptomics-into-the-clinic
#17
REVIEW
Yongxing Du, Bangbo Zhao, Ziwen Liu, Xiaoxia Ren, Wenjing Zhao, Zongze Li, Lei You, Yupei Zhao
Pancreatic cancer remains one of the most lethal malignancies, and insights into both personalized diagnosis and intervention of this disease are urgently needed. The rapid development of sequencing technologies has enabled the successive completion of a series of genetic and epigenetic sequencing studies of pancreatic cancer. The mutational landscape of pancreatic cancer is generally portrayed in terms of somatic mutations, structural variations, epigenetic alterations and the core signaling pathways. In recent years, four significant molecular subtype classifications of pancreatic cancer have been proposed based on the expression of transcription factors and downstream targets or the distribution of structural rearrangements...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#18
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28358303/a-novel-bio-psychosocial-behavioral-treatment-model-in-schizophrenia
#19
REVIEW
Yong-Ku Kim, Joonho Choi, Seon-Cheol Park
Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well...
March 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28357066/association-of-two-synonymous-splicing-associated-cpg-single-nucleotide-polymorphisms-in-calpain-10-and-solute-carrier-family-2-member-2-with-type-2-diabetes
#20
Maria Karambataki, Andigoni Malousi, Georgios Tzimagiorgis, Constantinos Haitoglou, Aikaterini Fragou, Elisavet Georgiou, Foteini Papadopoulou, Gerasimos E Krassas, Sofia Kouidou
Coding synonymous single nucleotide polymorphisms (SNPs) have attracted little attention until recently. However, such SNPs located in epigenetic, CpG sites modifying exonic splicing enhancers (ESEs) can be informative with regards to the recently verified association of intragenic methylation and splicing. The present study describes the association of type 2 diabetes (T2D) with the exonic, synonymous, epigenetic SNPs, rs3749166 in calpain 10 (CAPN10) glucose transporter (GLUT4) translocator and rs5404 in solute carrier family 2, member 2 (SLC2A2), also termed GLUT2, which, according to prior bioinformatic analysis, strongly modify the splicing potential of glucose transport-associated genes...
February 2017: Biomedical Reports
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