scholarly journals Somatic mutations in epigenetic regulation genes detected by NGS in gastric tumors

2020 ◽  
pp. 75-76
Author(s):  
М.В. Немцова ◽  
А.И. Калинкин ◽  
Е.Б. Кузнецова ◽  
Е.А. Алексеева ◽  
И.В. Буре ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Epigenetic Regulation ◽  
Somatic Mutations ◽  
Prognostic Markers ◽  
Epigenetic Mechanisms ◽  
Clinical Marker ◽  
Mutational Profiling ◽  
Cell Life ◽  
First Results

Эпигенетические механизмы регулируют структуру хроматина и создают устойчивые закономерности экспрессии генов в процессе жизни клеток. Нарушение эпигенетической регуляции играет значительную роль в канцерогенезе, инвазии, рецидивировании и метастазировании опухолей и может служить полезным клиническим маркером. Мутационное профилирование генов эпигенетической регуляции в опухолевых образцах рака желудка позволит определить новые клинические и прогностические маркеры и дополнительные таргеты для лечения пациентов. В статье представлены первые результаты исследования соматических мутаций в генах эпигенетической регуляции, проведенного методом NGS. Epigenetic mechanisms regulate chromatin structure and create stable patterns of gene expression during cell life. Violation of epigenetic regulation plays a significant role in carcinogenesis, invasion, recurrence and metastasis of tumors, and can serve as a useful clinical marker. Mutational profiling of epigenetic regulation genes in tumor samples of gastric cancer will allow us to identify new clinical and prognostic markers and additional targets for the treatment of patients with gastric cancer. This article presents the first results of a study of somatic mutations in the epigenetic regulation genes carried out using NGS.

scholarly journals Mutations in Epigenetic Regulation Genes in Gastric Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4586
Author(s):  
Marina V. Nemtsova ◽  
Alexey I. Kalinkin ◽  
Ekaterina B. Kuznetsova ◽  
Irina V. Bure ◽  
Ekaterina A. Alekseeva ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Chromatin Remodeling ◽  
Epigenetic Regulation ◽  
Somatic Mutations ◽  
Distant Metastases ◽  
Clinical Markers ◽  
Signet Ring Cells ◽  
Mutational Profiling ◽  
Signet Ring ◽  
Epigenetic Processes

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority (n = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority (n = 41), in histone modifier genes, among which mutations were most commonly found in KMT2D and KMT2C. Somatic mutations in KMT2D, KMT2C, ARID1A and CHD7 were mutually exclusive (p = 0.038). Mutations in ARID1A were associated with distant metastases (p = 0.03). The overall survival of patients in the group with metastases and in the group with tumors with signet ring cells was significantly reduced in the presence of mutations in epigenetic regulation genes (p = 0.036 and p = 0.041, respectively). Separately, somatic mutations in chromatin remodeling genes correlate with low survival rate of patients without distant metastasis (p = 0.045) and in the presence of signet ring cells (p = 0.0014). Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts.

scholarly journals Integrating Genetic and Transcriptomic Data to Reveal Pathogenesis and Prognostic Markers of Pancreatic Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaisong Bai ◽  
Tong Zhao ◽  
Yilong Li ◽  
Xinjian Li ◽  
Zhantian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Adenocarcinoma ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Variation ◽  
The Cancer Genome Atlas ◽  
Driver Genes

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients’ survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.

scholarly journals Novel Prognostic Biomarkers in Gastric Cancer: CGB5, MKNK2, and PAPPA2

2021 ◽  
Vol 11 ◽  
Author(s):  
Min Qin ◽  
Zhihai Liang ◽  
Heping Qin ◽  
Yifang Huo ◽  
Qing Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Regression Analysis ◽  
Immune Cells ◽  
Prognostic Model ◽  
Prognostic Markers ◽  
Immune Cell ◽  
Risk Group ◽  
P Value ◽  
Expression Data

IntroductionGastric cancer is one of the most common malignant tumors of the digestive tract. However, there are no adequate prognostic markers available for this disease. The present study used bioinformatics to identify prognostic markers for gastric cancer that would guide the clinical diagnosis and treatment of this disease.Materials and MethodsGene expression data and clinical information of gastric cancer patients along with the gene expression data of 30 healthy samples were downloaded from the TCGA database. The initial screening was performed using the WGCNA method combined with the analysis of differentially expressed genes, which was followed by univariate analysis, multivariate COX regression analysis, and Lasso regression analysis for screening the candidate genes and constructing a prognostic model for gastric cancer. Subsequently, immune cell typing was performed using CIBERSORT to analyze the expression of immune cells in each sample. Finally, we performed laboratory validation of the results of our analyses using immunohistochemical analysis.ResultsAfter five screenings, it was revealed that only three genes fulfilled all the screening requirements. The survival curves generated by the prognostic model revealed that the survival rate of the patients in the high-risk group was significantly lower compared to the patients in the low-risk group (P-value < 0.001). The immune cell component analysis revealed that the three genes were differentially associated with the corresponding immune cells (P-value < 0.05). The results of immunohistochemistry also support our analysis.ConclusionCGB5, MKNK2, and PAPPA2 may be used as novel prognostic biomarkers for gastric cancer.

scholarly journals Kynurenine, 3-OH-kynurenine, and anthranilate are nutrient metabolites that alter H3K4 trimethylation and H2AS40 O-GlcNAcylation at hypothalamus-related loci

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Koji Hayakawa ◽  
Kenta Nishitani ◽  
Satoshi Tanaka
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Epigenetic Modification ◽  
Neural Cells ◽  
Epigenetic Mechanisms ◽  
Post Translational Modifications ◽  
H3k4 Trimethylation ◽  
Expression Of Genes ◽  
Nutritional Conditions ◽  
Hypothalamic Function

AbstractEpigenetic mechanisms can establish and maintain mitotically stable patterns of gene expression while retaining the DNA sequence. These mechanisms can be affected by environmental factors such as nutrients. The importance of intracellular dosages of nutrient metabolites such as acetyl coenzyme A and S-adenosylmethionine, which are utilized as donors for post-translational modifications, is well-known in epigenetic regulation; however, the significance of indirect metabolites in epigenetic regulation is not clear. In this study, we screened for metabolites that function as epigenetic modulators. Because the expression of genes related to hypothalamic function is reportedly affected by nutritional conditions, we used a neural cell culture system and evaluated hypothalamic-linked loci. We supplemented the culture medium with 129 metabolites separately during induction of human-iPS-derived neural cells and used high-throughput ChIP-qPCR to determine the epigenetic status at 37 hypothalamus-linked loci. We found three metabolites (kynurenine, 3-OH-kynurenine, and anthranilate) from tryptophan pathways that increased H3K4 trimethylation and H2AS40 O-GlcNAcylation, resulting in upregulated gene expression at most loci, except those encoding pan-neural markers. Dietary supplementation of these three metabolites and the resulting epigenetic modification were important for stability in gene expression. In conclusion, our findings provide a better understanding of how nutrients play a role in epigenetic mechanisms.

M1906 Gene Expression Profiling of Metaplastic Lineages Identifies Novel Prognostic Markers in Early Stage Gastric Cancer

2010 ◽  
Vol 138 (5) ◽  
pp. S-436-S-437 ◽  
Author(s):  
Hyuk-Joon Lee ◽  
Ki Taek Nam ◽  
Heae Surng Park ◽  
Bonnie LaFleur ◽  
Hiroyuki Aburatani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prognostic Markers ◽  
Early Stage

Epigenetic Mechanisms Mediate Nicotine-Induced Reward and Behaviour in Zebrafish

2021 ◽  
Vol 19 ◽  
Author(s):  
Maria Paula Faillace ◽  
Ramón O. Bernabeu
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Histone Deacetylases ◽  
Dna Methyltransferase ◽  
Dopamine Neurons ◽  
Epigenetic Mechanisms ◽  
Chemical Modifications ◽  
Simultaneous Treatment ◽  
Polymerase Binding

: Nicotine induces long-term changes in the neural activity of the mesocorticolimbic reward pathway structures. The mechanisms involved in this process have not been fully characterized. The hypothesis discussed here proposed that epigenetic regulation participates in installing persistent adaptations and long-lasting synaptic plasticity generated by nicotine action on the mesolimbic dopamine neurons of zebrafish. The epigenetic mechanisms induced by nicotine entail histone and DNA chemical modifications, which have been described to lead to changes in gene expression. Among the enzymes that catalyze epigenetic chemical modifications, histone deacetylases (HDACs) remove acetyl groups from histones, thereby facilitating DNA relaxation and making DNA more accessible to gene transcription. DNA methylation, which is dependent on DNA methyltransferase (DNMTs) activity, inhibits gene expression by recruiting several methyl binding proteins that prevent RNA polymerase binding to DNA. In zebrafish, phenylbutyrate (PhB), an HDAC inhibitor, abolishes nicotine rewarding properties together with a series of typical reward-associated behaviors. Furthermore, PhB and nicotine alter long- and short-term object recognition memory in zebrafish, respectively. Regarding DNA methylation effects, a methyl group donor L-methionine (L-met) was found to dramatically reduce nicotine-induced conditioned place preference (CPP) in zebrafish. Simultaneous treatment with DNMT inhibitor 5-aza-2’-deoxycytidine (AZA) was found to reverse the L-met effect on nicotine-induced CPP as well as nicotine reward-specific impact on genetic expression in zebrafish. Therefore, pharmacological interventions that modulate gene expression epigenetic regulation should be considered a potential therapeutic method to treat nicotine addiction.

scholarly journals Dynamic changes in DNA methylation during seahorse (Hippocampus reidi) postnatal development and settlement

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Paula Suarez-Bregua ◽  
Sofia Rosendo ◽  
Pilar Comesaña ◽  
Lucia Sánchez-Ruiloba ◽  
Paloma Morán ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Postnatal Development ◽  
Expression Analysis ◽  
Epigenetic Regulation ◽  
Regulation Of Gene Expression ◽  
Age Groups ◽  
Dna Methyltransferases ◽  
Epigenetic Mechanisms ◽  
Competent Larva

Abstract Introduction Most living marine organisms have a biphasic life cycle dependent on metamorphosis and settlement. These critical life-history events mean that a developmentally competent larva undergoes a range of coordinated morphological and physiological changes that are in synchrony with the ecological transition from a pelagic to a benthonic lifestyle. Therefore, transition from a pelagic to a benthonic habitat requires multiple adaptations, however, the underlying mechanisms regulating this process still remains unclear. Epigenetic regulation and specifically DNA methylation, has been suggested to be particularly important for organisms to adapt to new environments. Seahorses (Family Syngnathidae, Genus Hippocampus) are a fascinating group of fish, distinguished by their unique anatomical features, reproductive strategy and behavior. They are unique among vertebrate species due to their “male pregnancy”, where males nourish developing embryos and larvae in a brood pouch until hatching and parturition occurs. After birth, free-swimming offspring are pelagic and subsequently they change into a demersal lifestyle. Therefore, to begin to address the question whether epigenetic processes could be involved in the transition from a planktonic to a benthonic lifestyle observed in seahorses, we studied global DNA methylation profiles in a tropical seahorse species (Hippocampus reidi) during postnatal development and settlement. Results We performed methylation-sensitive amplified polymorphism (MSAP) along with quantitative expression analysis for genes suggested to be involved in the methylation machinery at six age groups: 1, 5, 10, 20, 30 and 40 days after male’s pouch release (DAR). Results revealed that the H. reidi genome has a significantly different DNA methylation profile during postnatal development and settlement on demersal habitats. Moreover, gene expression analysis showed up- and down-regulation of specific DNA methyltransferases (DNMTs) encoding genes. Conclusion Our data show that the differences in the DNA methylation patterns seen among developmental stages and during the transition from a pelagic to a benthonic lifestyle suggest a potential for epigenetic regulation of gene expression (through DNA methylation) in this species. Therefore, epigenetic mechanisms could be necessary for seahorse settlement. Nevertheless, if these epigenetic mechanisms come from internal or if they are initiated via external environmental cues should be further investigated.

GLIOBLASTOMA MULTIFORME: PATHOGENESIS AND MOLECULAR MARKERS

2017 ◽  
Vol 63 (5) ◽  
pp. 695-702
Author(s):  
Oleg Kit ◽  
Dmitriy Vodolazhskiy ◽  
Yelena Frantsiyants ◽  
Svetlana Panina ◽  
E. Rastorguev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Tumor ◽  
Molecular Markers ◽  
Glioblastoma Multiforme ◽  
Somatic Mutations ◽  
Web Of Science ◽  
Molecular Subtypes ◽  
Regulation Of Gene Expression ◽  
Signal Pathways ◽  
Poorly Differentiated

Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor with nearly 100 % rate of recurrence and unfavorable prognosis. The aim of the present review is to analyze recent studies and experimental results (Scopus, Web of Science, PubMed) concerning somatic mutations in glioblastoma, aberrant regulation of gene expression of signal pathways including EGFR, TGFß, etc. and markers for GBM progression. Particularly the molecular subtypes of glioblastoma and NGS results are considered in this review.

Magnesium-dependent Phosphatase (MDP) 1 is a Potential Suppressor of Gastric Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 817-827
Author(s):  
Jianbo Zhu ◽  
Lijuan Deng ◽  
Baozhen Chen ◽  
Wenqing Huang ◽  
Xiandong Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cell Proliferation ◽  
Protein C ◽  
Biological Function ◽  
Prognostic Markers ◽  
Biological Effects ◽  
Signal Transducer ◽  
Gastric Cancer Cells ◽  
Transcription 3

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.

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