DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis

Abstract The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

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Role of DNA Methylation in the Development of Diffuse-Type Gastric Cancer

Digestion ◽

10.1159/000320453 ◽

2011 ◽

Vol 83 (4) ◽

pp. 241-249 ◽

Cited By ~ 32

Author(s):

Eiichiro Yamamoto ◽

Hiromu Suzuki ◽

Hiroyuki Takamaru ◽

Hiroyuki Yamamoto ◽

Minoru Toyota ◽

...

Keyword(s):

Gastric Cancer ◽

Dna Methylation ◽

Diffuse Type ◽

Diffuse Type Gastric Cancer

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Frequent CLDN18-ARHGAP fusion in highly metastatic diffuse-type gastric cancer with relatively early onset

Oncotarget ◽

10.18632/oncotarget.25464 ◽

2018 ◽

Vol 9 (50) ◽

pp. 29336-29350 ◽

Cited By ~ 14

Author(s):

Atsushi Tanaka ◽

Shumpei Ishikawa ◽

Tetsuo Ushiku ◽

Sho Yamazawa ◽

Hiroto Katoh ◽

...

Keyword(s):

Gastric Cancer ◽

Early Onset ◽

Diffuse Type ◽

Diffuse Type Gastric Cancer

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Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation

10.21203/rs.3.rs-351723/v2 ◽

2021 ◽

Author(s):

yinggang hua ◽

yanling liu ◽

long li ◽

guoyan liu

Keyword(s):

Gastric Cancer ◽

Dna Methylation ◽

Promoter Region ◽

Methylation Status ◽

Diffuse Gastric Cancer ◽

Normal Tissues ◽

The Difference ◽

Diffuse Type Gastric Cancer ◽

Cancer Tissues ◽

Erk Signal Pathway

Abstract Background P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, its DNA methylation status or even the corresponding regulatory mechanism remains unknown. Methods In this study, DNA methylation chip was used to profile the genome-wide DNA methylation level in gastric cancer tissues. Then validated by the bioinformatics analysis in the TCGA database, Immunohistochemistry staining data obtained from the HPA database to verify the difference in protein expression between normal tissues and tumor tissues . Results The promoter region of P2RY1 was found to be highly methylated with 4 hypermethylated sites (|Δβ value| >0.2) in diffuse gastric cancer and the expression level of P2RY1 is relatively low compared with non-cancerous tissues. We also showed that MRS2365, a selective agonist of the P2RY1 receptor, can induce phosphorylation of ERK1/2, inhibit cell proliferation/migration and induce apoptosis. Conclusion High DNA methylation in the promoter region of P2RY1 may have contributed to the reduced expression of P2RY1’s mRNA, which is likely responsible for the “aggressive” nature of the diffuse type gastric cancer.

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SU10THE DNA METHYLATION PROFILE IN BDNF EXON 1 PROMOTER REGION IN DRUG DEFAULT PATIENTS OF BIPOLAR AFFECTIVE DISORDERS: AN INDIAN STUDY

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2018.08.374 ◽

2019 ◽

Vol 29 ◽

pp. S1273

Author(s):

Sydney Moirangthem ◽

Sanjeev Jain ◽

Meera Purushottam ◽

Biju Viswanath

Keyword(s):

Dna Methylation ◽

Affective Disorders ◽

Promoter Region ◽

Methylation Profile ◽

Indian Study ◽

Dna Methylation Profile ◽

Exon 1 ◽

Bipolar Affective Disorders

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Mo1557 DNA Methylation in Gastric Mucosae is Associated With the Severity of Mucosal Inflammation Involving the Risk of Diffuse-Type Gastric Cancer

Gastroenterology ◽

10.1016/s0016-5085(12)62412-3 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-628

Author(s):

Takeichi Yoshida ◽

Jun Kato ◽

Takao Maekita ◽

Satoshi Yamashita ◽

Shotaro Enomoto ◽

...

Keyword(s):

Gastric Cancer ◽

Dna Methylation ◽

Mucosal Inflammation ◽

Diffuse Type ◽

Diffuse Type Gastric Cancer

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Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.1255 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

G Benincasa ◽

C Schiano ◽

T Infante ◽

M Franzese ◽

R Casale ◽

...

Keyword(s):

Dna Methylation ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cpg Island ◽

Methylation Profile ◽

Integrated Analysis ◽

Funding Source ◽

Relevant Parameter ◽

Cardiac Computed Tomography Angiography ◽

Dna Methylation Profile

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

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DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Communications Biology ◽

10.1038/s42003-020-01469-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Vanessa Lakis ◽

◽

Rita T. Lawlor ◽

Felicity Newell ◽

Ann-Marie Patch ◽

...

Keyword(s):

Dna Methylation ◽

Neuroendocrine Tumors ◽

Methylation Profile ◽

Pancreatic Neuroendocrine Tumors ◽

Wild Type ◽

Genomic Information ◽

Chromosome 11 ◽

Dna Methylation Profile ◽

Methylation Patterns ◽

Recurrent Patterns

AbstractHere we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

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