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

Jeong Mo Bae, So Hyun Shin, Hyeongju Kwon, Seog Yun Park, Myeong Cherl Kook, Young Woo Kim, Nam Yun Cho, Nayoung Kim, Tae You Kim, Donguk Kim, Gyeong Hoon Kang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1323-1331
Number of pages9
JournalInternational Journal of Cancer
Volume131
Issue number6
DOIs
Publication statusPublished - 2012 Sep 15

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Methylation
Stomach
Carcinogenesis
Stomach Neoplasms
Adenoma
Metaplasia
Biomarkers
CpG Islands
DNA
Helicobacter Infections
Gastritis
Human Genome
DNA Methylation
Helicobacter pylori
Multivariate Analysis
Biopsy
Polymerase Chain Reaction
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Bae, Jeong Mo ; Shin, So Hyun ; Kwon, Hyeongju ; Park, Seog Yun ; Kook, Myeong Cherl ; Kim, Young Woo ; Cho, Nam Yun ; Kim, Nayoung ; Kim, Tae You ; Kim, Donguk ; Kang, Gyeong Hoon. / ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. In: International Journal of Cancer. 2012 ; Vol. 131, No. 6. pp. 1323-1331.
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Bae, JM, Shin, SH, Kwon, H, Park, SY, Kook, MC, Kim, YW, Cho, NY, Kim, N, Kim, TY, Kim, D & Kang, GH 2012, 'ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications', International Journal of Cancer, vol. 131, no. 6, pp. 1323-1331. https://doi.org/10.1002/ijc.27369

ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. / Bae, Jeong Mo; Shin, So Hyun; Kwon, Hyeongju; Park, Seog Yun; Kook, Myeong Cherl; Kim, Young Woo; Cho, Nam Yun; Kim, Nayoung; Kim, Tae You; Kim, Donguk; Kang, Gyeong Hoon.

In: International Journal of Cancer, Vol. 131, No. 6, 15.09.2012, p. 1323-1331.

Research output: Contribution to journalArticle

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AU - Bae, Jeong Mo

AU - Shin, So Hyun

AU - Kwon, Hyeongju

AU - Park, Seog Yun

AU - Kook, Myeong Cherl

AU - Kim, Young Woo

AU - Cho, Nam Yun

AU - Kim, Nayoung

AU - Kim, Tae You

AU - Kim, Donguk

AU - Kang, Gyeong Hoon

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N2 - 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.

AB - 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.

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