scholarly journals DNA co-methylation networks outline the structure and remodeling dynamics of colorectal cancer epigenome

2018 ◽  
Author(s):  
Izaskun Mallona ◽  
Susanna Aussó ◽  
Anna Díez-Villanueva ◽  
Víctor Moreno ◽  
Miguel A. Peinado
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Colon Cancer ◽  
Genome Organization ◽  
Tumor Tissue ◽  
Network Modeling ◽  
Genome Architecture ◽  
Epigenetic Mark ◽  
And Function ◽  
Unique Signature

AbstractEpigenomic plasticity is interconnected with chromatin structure and gene regulation. In tumor progression, orchestrated remodeling of genome organization accompanies the acquisition of malignant properties. DNA methylation, a key epigenetic mark extensively altered in cancer, is also linked to genome architecture and function. Based on this association, we postulate that the dissection of long-range co-methylation structure unveils cancer cell’s genome architecture remodeling.We applied network-modeling of DNA methylation co-variation in two colon cancer cohorts and found abundant and consistent transchromosomal structures in both normal and tumor tissue. Normal-tumor comparison indicated substantial remodeling of the epigenome covariation and revealed novel genomic compartments with a unique signature of DNA methylation rank inversion.

scholarly journals Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xi Yang ◽  
Quan Qi ◽  
Yuefen Pan ◽  
Qing Zhou ◽  
Yinhang Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Peripheral Blood ◽  
Strong Correlation ◽  
Tumor Tissue ◽  
Cell Populations

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.

scholarly journals DNA modifications in the mammalian brain

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130512 ◽  
Author(s):  
Jaehoon Shin ◽  
Guo-li Ming ◽  
Hongjun Song
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Genomic Imprinting ◽  
Mammalian Brain ◽  
Epigenetic Mark ◽  
Mammalian Development ◽  
Dna Modifications ◽  
Dna Elements ◽  
And Function ◽  
Neuronal Functions

DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function.

scholarly journals Whole genome bisulfite sequencing reveals a sparse, but robust pattern of DNA methylation in the Dictyostelium discoideum genome

2017 ◽  
Author(s):  
Jacob L. Steenwyk ◽  
James St. Denis ◽  
Jacqueline M. Dresch ◽  
Denis A. Larochelle ◽  
Robert A. Drewell
Keyword(s):  
Dna Methylation ◽  
Dictyostelium Discoideum ◽  
Dna Methyltransferase ◽  
Model Organism ◽  
Epigenetic Mark ◽  
Whole Genome ◽  
Protein Coding ◽  
Genome Bisulfite Sequencing ◽  
Chromatin Structural ◽  
And Function

AbstractDNA methylation, the addition of a methyl (CH3) group to a cytosine residue, is an evolutionarily conserved epigenetic mark involved in a number of different biological functions in eukaryotes, including transcriptional regulation, chromatin structural organization, cellular differentiation and development. In the slime mold Dictyostelium, previous studies have shown the existence of a DNA methyltransferase (DNMA) belonging to the DNMT2 family, but the extent and function of 5-methyl-cytosine in the genome is unclear. Here we present the whole genome DNA methylation profile of Dictyostelium discoideum using deep coverage, replicate sequencing of bisulfite converted gDNA extracted from post-starvation cells. We find an overall very low level of DNA methylation, occurring at only 462 out of the ~7.5 million (0.006%) cytosines in the genome. Despite this sparse profile, significant methylation can be detected at 51 of these sites in replicate experiments, suggesting they are robust targets for DNA methylation. These 5-methyl-cytosines are associated with a broad range of protein-coding genes, tRNA-encoding genes and retrotransposable elements. Our data provides evidence of a minimal, but functional, methylome in Dictyostelium, thereby making Dictyostelium a candidate model organism to further investigate the evolutionary function of DNA methylation.

scholarly journals Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chih-Hsiung Hsu ◽  
Cheng-Wen Hsiao ◽  
Chien-An Sun ◽  
Wen-Chih Wu ◽  
Tsan Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Tumor Tissue ◽  
Clinical Stage ◽  
Methylation Status ◽  
Aberrant Methylation ◽  
Event Free Survival ◽  
Free Survival ◽  
Normal Tissues ◽  
Colorectal Cancer Patients

AbstractThis study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/advanced) were 8.04 (95% CI, 2.80–23.1; P for trend <0.01) and 8.01 (95% CI, 1.92–33.4; P for trend <0.01) in normal and tumor tissue, respectively. DNA methylation status was significantly associated with poor prognosis outcome. This finding in the matched normal tissues of colorectal cancer patients could be an alternative source of prognostic markers to assist clinical decision making.

scholarly journals Effects of the lncRNA ENST00000623984 on colon cancer and the biological characteristics of colon cancer cells

2021 ◽  
Vol 65 (3) ◽  
Author(s):  
Zhi-bao Liu ◽  
Jing-hua Zhang ◽  
Jing-hua Gao ◽  
Jian Shi
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Viability ◽  
Cell Cycle Progression ◽  
Tumor Tissue ◽  
Proliferation Rate ◽  
Migration And Invasion ◽  
Sirna Transfection ◽  
Cycle Progression ◽  
Lovo Cells

The aim of this study was to explore the effects of the lncRNA ENST00000623984 on colorectal cancer. In this study, the expression levels of ENST000000623984 were first examined in tumor tissue and adjacent normal tissue from 40 patients with colorectal cancer and LoVo cells using quantitative real-time PCR. By siRNA transfection, ENST00000623984 expression was knocked down. Using flow cytometry, cell cycle progression and cell viability were examined in basal and knockdown LoVo cells. The CCK-8 assay was used to assess the cell proliferation rate, and the Transwell assay was used to determine the migration and invasion abilities. The ENST000000623984 expression level was increased in colorectal cancer. Knockdown of ENST000000623984 reduced cell viability, proliferation rate, cell migration and invasion. These results suggested that lncRNA ENST000000623984 may be involved in colorectal cancer development.

A multi-gene colorectal cancer liquid biopsy with >90% accuracy in diagnosis and assessment of disease status.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16079-e16079
Author(s):  
Irvin Mark Modlin ◽  
Mark S. Kidd ◽  
Alexandra Kitz ◽  
Ignat A. Drozdov ◽  
Anna Malczewska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Surgical Resection ◽  
Cell Lines ◽  
Stable Disease ◽  
Liquid Biopsy ◽  
Clinical Utility ◽  
Tumor Tissue ◽  
Blood Gene Expression

e16079 Background: There are few blood-based biomarkers for colorectal cancer (CRC). We report a 13-gene colon cancer circulating-free mRNA to diagnose CRC. Clinical utility was assessed in surgical and chemotherapy patients. Methods: Gene identification/validation: Publicly available colon cancer transcriptomes (E-MTAB-57) to identify candidate markers using gene co-expression network enrichment, differential expression and functional enrichment analyses. Cell line/tumor tissue gene expression: Candidate gene expression was evaluated in 3 CRC cell-lines (LOVO, LS-180 and COLO320DM) and surgical resection samples (CRC adenocarcinomas: n= 33) and biomarkers validated in the TCGA-COAD database ( n= 261 adenocarcinomas, 41 mucinous adenocarcinomas). Blood gene expression: CRC set (cancers: n= 312, controls n= 117) and a CRC artificial intelligence model constructed. Normalized gene expression algorithmically scored (0-100). Matched tumor/ blood samples were available in 33 patients. RECIST criteria Clinical score assessment: Score utility was assessed in surgical and treated cohorts: Surgical: n= 37, follow>7 days. Chemotherapy: n= 75; stable disease (SD): n= 20, progressive disease (PD): n= 55). The relationship to CEA and CA-19-9 were assessed. Statistics: Non-parametric (Mann-Whitney), Pearson-correlation, Fisher’s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis: Thirteen candidate CRC genes blood were identified. Cell lines and tumor tissue: Expression levels were significantly elevated ( p< 0.001, 20-100-fold) in cell lines and CRC tumors. All 13 markers were confirmed in TCGA-COAD samples (average TPM ranged from 692-4405). Blood gene expression: All 13 CRC marker genes were identified in CRC blood. Levels were 54.4±1.5 ( p< 0.0001) compared to controls (9.5±1.7); AUROC:0.91±0.02, accuracy 90.5% (sensitivity 93.1%, specificity 81.2%). The matched tissue/blood correlation was r = 0.80 ( p= 0.002). Clinical Utility: In the surgical cohort, accuracy was 100% vs CEA (35%) or CA-19-9 (17%) (both p< 0.0001). Resection (R0–92%) significantly decreased levels (47±2) at follow-up ( p< 0.006). In the treated cohort, levels were elevated in PD (63±4.1) vs SD (30±3.2, p< 0.0001). Conclusions: A CRC gene marker panel in blood identified colon cancer with a diagnostic accuracy of 91%. This was significantly greater than CEA or CA-19 in CRCs. Surgical resection decreased levels. CRC score was elevated in progressive vs stable disease. A colorectal cancer liquid biopsy will facilitate image-based management.

scholarly journals The exploration of N6-deoxyadenosine methylation in mammalian genomes

2021 ◽  
Author(s):  
Xuwen Li ◽  
Zijian Zhang ◽  
Xinlong Luo ◽  
Jacob Schrier ◽  
Andrew D. Yang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Regulatory Mechanism ◽  
Epigenetic Mark ◽  
Dna Modification ◽  
Biological Processes ◽  
Environmental Stress Response ◽  
Mammalian Genomes ◽  
Higher Eukaryotes ◽  
And Function ◽  
Major Progress

AbstractN6-methyladenine (N6-mA, m6dA, or 6mA), a prevalent DNA modification in prokaryotes, has recently been identified in higher eukaryotes, including mammals. Although 6mA has been well-studied in prokaryotes, the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood. Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes, from transposable-element suppression to environmental stress response. Here, we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes, predominantly mammals.

scholarly journals Evolutionary analysis of DNA methyltransferases in microeukaryotes: Insights from the model diatom Phaeodactylum tricornutum

2021 ◽  
Author(s):  
ANTOINE HOGUIN ◽  
Ouardia Ait Mohamed ◽  
Chris Bowler ◽  
Auguste Genovesio ◽  
Fabio RJ Vieira ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Phaeodactylum Tricornutum ◽  
Dna Methyltransferase ◽  
Transcriptional Control ◽  
Dna Methyltransferases ◽  
Epigenetic Mark ◽  
Evolutionary Analysis ◽  
And Function ◽  
Dnmt Family

Cytosine DNA methylation is an important epigenetic mark in eukaryotes that is involved in the transcriptional control of mainly transposable elements in mammals, plants, and fungi. Eukaryotes encode a diverse set of DNA methyltransferases that were iteratively acquired and lost during evolution. The Stramenopiles-Alveolate-Rhizaria (SAR) lineages are a major group of ecologically important marine microeukaryotes that include the main phytoplankton classes such as diatoms and dinoflagellates. However, little is known about the diversity of DNA methyltransferases and their role in the deposition and maintenance of DNA methylation in microalgae. We performed a phylogenetic analysis of DNA methyltransferase families found in marine microeukaryotes and show that they encode divergent DNMT3, DNMT4, DNMT5 and DNMT6 enzymes family revisiting previously established phylogenies. Furthermore, we reveal a novel group of DNMTs with three classes of enzymes within the DNMT5 family. Using a CRISPR/Cas9 strategy we demonstrate that the loss of the DNMT5 gene correlates with a global depletion of DNA methylation and overexpression of transposable elements in the model diatom Phaeodactylum tricornutum. The study provides a pioneering view of the structure and function of a DNMT family in the SAR supergroup.

scholarly journals Adenokarsinoma Kolon: Laporan Kasus

e-CliniC ◽  
2020 ◽  
Vol 8 (2) ◽  
Author(s):  
Mersy S. Padang ◽  
Luciana Rotty
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Colorectal ◽  
Tumor Tissue ◽  
Internal Hemorrhoid ◽  
Pathological Examination ◽  
Colon Tissue ◽  
Extensive Resection ◽  
Bowel Movements ◽  
Total Cancer

Abstract: Colorectal cancer (CRC) is a malignancy originated from the colon tissue which starts in the large intestine and rectum. In 2018, colorectal cancer was ranked fourth of the total malignancy in Indonesia with the number of cases of 30,017 (8.6% of the total cancer cases in Indonesia). We reported a case of colon cancer (adenocarcinoma) in a female aged 34 years. Diagnosis was based on anamnesis of the presence of liquid bowel movements along with blood, intermittent abdominal pain, and change of defecation pattern. Physical examination obtained tenderness in epigastric and hypochondriac right button regions. Colonoscopy was performed and revealed a colonic tumor suspicious of adenocarcinoma, suspected chronic colitis, and internal hemorrhoid. Pathological examination of the tumor tissue resulted in colonic adenocarcinoma (moderate differentiation). The management of this patient was extensive resection with anastomosis and was planned for adjuvant therapy.Keywords: adenocarcinoma colon cancer, colorectal cancer Abstrak: Kanker kolorektal (KKR) adalah keganasan yang berasal dari jaringan usus besar, yang menyerang usus besar dan rektum. Di Indonesia pada tahun 2018, kanker kolorektal menduduki posisi keempat dari keseluruhan diagnosis kanker dengan jumlah kasus 30.017 (8,6% dari seluruh kasus kanker di Indonesia). Kami melaporkan sebuah kasus kanker kolon (adenokarsinoma) pada seorang perempuan usia 34 tahun. Diagnosis ditegakkan berdasarkan anamnesis adanya buang air besar cair diserta darah, nyeri perut hilang timbul, perubahan pola defekasi. Pada pemeriksaan fisik didapatkan nyeri tekan epigastrium dan nyeri tekan bagian hipocondria kanan. Pada pemeriksaan penunjang dilakukan kolonoskopi dan didapatkan hasil tumor kolon curiga adenocarcinoma, kolitis kronik curiga kolitis ulseratif, dan hemoroid interna. Hasil patologi anatomi dari kolonoskopi yaitu kolitis kronis dengan displasia kolon ascenden dan hasil patologi anatomi jaringan tumor berupa adenokarsinoma kolon (diferensiasi sedang). Tatalaksana yang diberikan untuk pada pasien ini berupa tindakan reseksi luas dengan anastomosis dan direncanakan untuk terapi adjuvan.Kata kunci: adenokarsinoma kolon, kanker kolorektal

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