Improved measurement of LINE-1 sequence methylation for cancer detection

Pobsook, Tuangtong; Subbalekha, Keskanya; Sannikorn, Phakdee; Mutirangura, Apiwat

doi:10.1016/j.cca.2010.10.030

Cited by 41 publications

(47 citation statements)

References 37 publications

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“…To improve the efficiency of detecting cancer DNA and to measure the overall methylation level, we recently classified LINE1s into 4 groups based on the methylation statuses of 2 CpG dinucleotides in each LINE-1 sequence. These 4 classes were hypermethylation ( m C m C), hypomethylation ( u C u C), and 2 forms of partial methylation ( m C u C and u C m C) (Pobsook, 2011;Kitkumthorn, 2012). We found that differences in the LINE-1 methylation pattern could be observed even if the overall levels were unchanged.…”

Section: Line-1 and Alu Methylation Patterns In Lymph Node Metastasesmentioning

confidence: 75%

“…We found that differences in the LINE-1 methylation pattern could be observed even if the overall levels were unchanged. Furthermore, partial methylation contributed to differences in the overall methylation levels between various normal tissue types, oral epithelium and white blood cells (Pobsook, 2011). Finally, for cancer DNA detection, % u C u C is more sensitive and specific than the methylation level (Pobsook, 2011;Kitkumthorn, 2012).…”

Section: Line-1 and Alu Methylation Patterns In Lymph Node Metastasesmentioning

confidence: 98%

“…These techniques were designed to detect 2 CpG dinucleotide sites, allowing us to determine not only the methylation level but also the methylation patterns of LINE-1 and Alu (Pobsook, 2011). At present, most quantitative methylation techniques, including pyrosequencing, can only measure the methylation level (usually from 3 CpG) and cannot distinguish specific LINE-1 and Alu methylation patterns.…”

Section: And Alu Methylation Patterns In Lymph Node Metastases Of Heamentioning

confidence: 99%

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LINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers

Kitkumthorn

Keelawat²,

Rattanatanyong³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Line-1 and Alu Methylation Patterns In Lymph Node Metastasesmentioning

confidence: 75%

Section: Line-1 and Alu Methylation Patterns In Lymph Node Metastasesmentioning

confidence: 98%

Section: And Alu Methylation Patterns In Lymph Node Metastases Of Heamentioning

confidence: 99%

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LINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers

Kitkumthorn

Keelawat²,

Rattanatanyong³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…44,48 In their recent study, Pobsook et al found that the methylation pattern of LINE-1 can distinguish cancer cell DNA from normal cell DNA in addition to the methylation level. 49 They performed a COBRA assay examining the methylation of two CpG sites of LINE-1; their method provides molecule-based information regarding the methylation statuses of the two CpG sites, enabling the classification of individual LINE-1 alleles into three groups according to the methylation pattern of the two CpG sites: hypomethylated, partially methylated, and hypermethylated LINE-1 loci. They found that the proportion of hypomethylated LINE-1 loci outperformed the overall methylation level of LINE-1 with respect to sensitivity and specificity of cancer detection.…”

Section: Discussionmentioning

confidence: 99%

“…They found that the proportion of hypomethylated LINE-1 loci outperformed the overall methylation level of LINE-1 with respect to sensitivity and specificity of cancer detection. 26,49 Although pyrosequencing is a well-established and validated method for quantifying methylation levels in individual CpG sites, it does not provide information regarding the moleculebased methylation status of multiple CpG sites or the proportion of hypomethylated LINE-1 loci. For the application of LINE-1 methylation status as a biomarker in clinical samples, a methodology enabling the rapid, reproducible, and quantitative assessment of LINE-1 methylation in large samples is required.…”

Section: Discussionmentioning

confidence: 99%

ALU and LINE‐1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications

Bae

Shin

Kwon

et al. 2012

Intl Journal of Cancer

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Focal CpG island hypermethylation and diffuse genomic hypomethylation signify the changes in the DNA methylation status in cancer cells. ALU and LINE-1 repetitive DNA elements comprise~28% of the human genome. PCR-based measurements of these repetitive DNA elements can be used as a surrogate marker of the genomewide methylation content. Our study aimed to identify the timing of ALU and LINE-1 hypomethylations during multistep gastric carcinogenesis and their prognostic implications in gastric cancer (GC). In our study, we analyzed the methylation statuses of ALU and LINE-1 in 249 cases of gastric biopsy samples and another independent set of 198 cases of advanced GC by pyrosequencing. Regardless of the Helicobacter pylori infection status, a significant decrease in the ALU methylation levels was noted during the transitions from chronic gastritis to intestinal metaplasia and from gastric adenoma to GC. LINE-1 methylation decreased during the transition from intestinal metaplasia to gastric adenoma and no further decrease occurred during the transition from gastric adenoma to GC. A low LINE-1 methylation status was strongly associated with poor prognosis in GC. A multivariate analysis revealed that LINE-1 methylation status was an independent prognostic factor. Our findings suggest that ALU and LINE-1 hypomethylations are early events during multistep gastric carcinogenesis. Furthermore, the LINE-1 methylation status can be used as a molecular biomarker to define a subset of GC patients with poor prognosis.Focal promoter CpG island hypermethylation and generalized genomic hypomethylation signify the changes in the DNA methylation status in human cancer cells. Promoter CpG island hypermethylation is an important mechanism that inactivates tumor suppressor and tumor-related genes; meanwhile, generalized genomic hypomethylation contributes to genomic or chromosomal instability.1-3 Genomic hypomethylation mainly affects repetitive transposable DNA elements, which comprise 45% of the human genome 4 ; these elements reside mainly in the intergenic and intronic regions of the genome and in noncoding and coding exons of the genome to a much lesser extent.5 Long interspersed nucleotide element-1 (LINE-1) and ALU are major constituents of interspersed DNA repeats, constituting $17% and 11% of the human genome, respectively. 4CpG sites located within LINE-1 and ALU are usually methylated in normal somatic tissues, a mechanism that is believed to have evolved as a major defense mechanism to repress these transposable genetic elements.6 Demethylation of transposable elements is hypothesized to facilitate genomic instability by leading to retrotransposition of transposable elements, hypomethylated genome-associated error-prone repair of replication-independent endogenous double-strand breaks, and dysregulation of DNA repair genes. [7][8][9][10][11] In addition to bringing about genomic structural variation, demethylation of transposable element promoters dysregulates gene expression by upregulating the transcription of genes l...

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Methylated DNA as Cancer Biomarkers in Circulation

Dakubo

2016

Cancer Biomarkers in Body Fluids

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Improved measurement of LINE-1 sequence methylation for cancer detection

Cited by 41 publications

References 37 publications

LINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers

LINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers

ALU and LINE‐1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications

Methylated DNA as Cancer Biomarkers in Circulation

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