Lower LINE-1 methylation is associated with promoter hypermethylation and distinct molecular features in gastric cancer

Epigenomics ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1651-1659
Author(s):  
Sayumi Tahara ◽  
Tomomitsu Tahara ◽  
Noriyuki Horiguchi ◽  
Masaaki Okubo ◽  
Tsuyoshi Terada ◽  
...  

Aim: To investigate the associations between LINE1 methylation, an indicator for genome-wide hypomethylation, molecular and clinicopathological characteristics of gastric cancer (GC) patients. Patients & methods: LINE1 methylation statuses were examined in paired cancerous, non-neoplastic mucosa from 217 GC and gastric mucosa from separate group of 224 noncancer patients. CpG island methylator phenotype, TP53 and KRAS mutation, MLH1 methylation status and promoter hypermethylation of GC related and H. pylori-related genes were examined. Results: Lower LINE1 methylation was observed in primary GC compared with non-neoplastic gastric mucosa and associated with CpG island methylator phenotype, TP53 mutation, MLH1 methylation and promoter hypermethylation of GC related and H. pylori-related genes. Conclusion: Lower LINE1 methylation correlates specific molecular subtypes and promoter hypermethylation in GC.

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130409 ◽  
Author(s):  
Kunitoshi Shigeyasu ◽  
Takeshi Nagasaka ◽  
Yoshiko Mori ◽  
Naosuke Yokomichi ◽  
Takashi Kawai ◽  
...  

2018 ◽  
Vol 109 (8) ◽  
pp. 2623-2625 ◽  
Author(s):  
Huashi Xiao ◽  
Jiaxin Fu ◽  
Masanobu Abe ◽  
Jiafu Ji ◽  
Liang Zong

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2229-2229
Author(s):  
Reid F. Thompson ◽  
Maria E. Figueroa ◽  
Ari M. Melnick ◽  
John M. Greally

Abstract Epigenetic changes (in particular, altered cytosine methylation) have been described in a variety of tumors. The CpG Island Methylator Phenotype (CIMP) is a well-known instance of this phenomenon wherein cytosine methylation is markedly dysregulated (normally hypomethylated loci shift to a methylated state). CIMP has been demonstrated in a number of different cancer types including hematological malignancies like AML. While methylation status has been studied predominantly at CpG islands, we used a novel assay (HELP; Khulan et al., Genome Res. 2006) to look for changes in cytosine methylation in large contiguous regions of the genome. We assessed global patterns of cytosine methylation by HELP analysis in a variety of tumor samples including leukemias and lymphomas. We found significant changes in the global methylation patterns of malignant cells, confirming prior observations of epigenetic dysregulation in these tumor types. We also discovered that the majority of the changes in cytosine methylation are occurring not at CpG islands but at other loci in the genome, including constitutively hypomethylated loci that we are finding to be candidate cis-regulatory sequences. We conclude that cytosine methylation changes in cancer occur much more extensively than analysis of CpG islands alone would indicate, and that the epigenetic dysregulation in cancer may be predominantly targeted to cis-regulatory sequences rather than to promoters.


2021 ◽  
Author(s):  
Ruixue Lei ◽  
Yanteng Zhao ◽  
Kai Huang ◽  
Qian Wang ◽  
Kangkang Wan ◽  
...  

Abstract BackgroudMethylated SDC2 and TFPI2 are applied frequently for the early detection of colorectal cancer (CRC). However, they often miss some positive samples, which directly affects their sensitivities, and the underlining mechanism is not well known.Methods:CRC samples from TCGA and GEO datasets were divided into three groups, Highmethylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Lowmethylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location, and microsatellite instable were then assessed between the three groups and verified in our custom cohort.ResultsSamples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration.Conclusions:The three methylation phenotypes identified based on SDC2 and TFPI2 methylation status showed extensive variations in tumor location, patient age, MSI and ECM biology processes, suggesting that these respective sides should be considered when developing new methylation-based biomarkers for CRC detection.


2011 ◽  
Vol 135 (6) ◽  
pp. 759-765
Author(s):  
So-Hyun Shin ◽  
Seog-Yun Park ◽  
Jae-Sung Ko ◽  
Nayoung Kim ◽  
Gyeong Hoon Kang

Abstract Context.—Helicobacter pylori infection is primarily acquired during childhood and persists throughout life in the absence of eradication with antibiotics. Helicobacter pylori infection induces methylation in the promoter CpG island loci in gastric epithelial cells. Thus, aberrant CpG island hypermethylation in gastric epithelial cells likely occurs early in life, although there are no existing data supporting this notion. Objectives.—To identify whether aberrant CpG island hypermethylation occurs in pediatric stomach mucosa in association with H pylori infection and to compare methylation profiles of samples from pediatric and adult stomach tissues. Design.—We analyzed pediatric (n  =  47) and adult (n  =  38) gastric mucosa samples for their methylation status in 12 promoter CpG island loci using the MethyLight assay and compared the number of methylated genes and the methylation levels in individual genes between H pylori–positive and H pylori–negative sample results and between pediatric and adult samples. Results.—The average number of methylated genes was significantly higher in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (3.4 versus 0.3, P &lt; .001) and in H pylori–infected adult samples than in H pylori–negative adult samples (7.6 versus 0.9, P &lt; .001). Seven genes showed significantly higher methylation levels in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (all values were P &lt; .05). Conclusions.—These results indicate that CpG island hypermethylation occurs in pediatric gastric mucosa in association with H pylori infection and that the genes affected by H pylori–associated hypermethylation were similar in pediatric and adult samples.


2011 ◽  
Vol 103 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Hua-Yun Chen ◽  
Bao-He Zhu ◽  
Chang-Hua Zhang ◽  
Dong-Jie Yang ◽  
Jian-Jun Peng ◽  
...  

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