title: ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications.
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.
authors: Department of Pathology, Second Stage Brain Korea Project and Seoul National University College of Medicine, Seoul, Korea.
authors: Jeong Mo
authors: JM
authors: Bae
authors: So-Hyun
authors: SH
authors: Shin
authors: Hyeong-Ju
authors: HJ
authors: Kwon
authors: Seog-Yun
authors: SY
authors: Park
authors: Myeong Cherl
authors: MC
authors: Kook
authors: Young-Woo
authors: YW
authors: Kim
authors: Nam-Yun
authors: NY
authors: Cho
authors: Nayoung
authors: N
authors: Kim
authors: Tae-You
authors: TY
authors: Kim
authors: Donguk
authors: D
authors: Kim
authors: Gyeong Hoon
authors: GH
authors: Kang
mesh_terms: D000368:Aged; D020087:Alu Elements / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology