Prognostic Implications of ALU and LINE-1 Hypomethylation in Gastric Cancer.
Jeong-Mo Bae, Hyeong-Ju Kwon, Seog-Yun Park, Myeong-Cherl Kook, Nam-Yun Cho, Gyeong-Hoon Kang. Seoul National University Hospital, Republic of Korea; National Cancer Center, Goyang-si, Republic of Korea; Cancer Research Institute, Seoul National University, Republic of Korea
Background: Changes in DNA methylation status in cancer cells are characterized by focal CpG island hypermethylation and diffuse genomic hypomethylation. ALU and LINE-1 repetitive DNA elements constitute about 28% of the human genome, and PCR-based measurements of these repetitive DNA elements can be used as a surrogate for genome-wide methylation content. Although repetitive DNA hypomethylation has been shown to be closely associated with poor prognosis in epithelial malignancies of some tissue types, little is known about the prognostic implications of ALU and LINE-1 hypomethylation in gastric cancer.
Design: In the present study, we analyzed the methylation status of repetitive DNA elements (ALU and LINE-1) and 16 cancer-specific DNA methylation markers in 195 cases of advanced gastric cancer using combined bisulfite restriction analysis and the MethyLight assay, respectively.
Results: Low methylation status of ALU or LINE-1 was closely associated with poor prognosis of gastric cancer, but multivariate analysis revealed that only ALU methylation status is an independent prognostic factor. When the combination of ALU and LINE-1 methylation status was analyzed, low ALU methylation status plus low LINE-1 methylation status defined a subset of gastric cancers that were closely associated with poor prognosis, and this was statistically significant upon multivariate analysis.
Conclusions: These findings suggest that the combination of ALU and LINE-1 methylation status could be used as a molecular biomarker to define a subset of gastric cancer patients with a poor prognosis.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 159, Tuesday Morning