LINE-1 Hypomethylation in Cancer Is Highly Variable and Inversely Correlated with Microsatellite Instability

• DOI: 10.1371/journal.pone.0000399
• Publication Date: 2007-05-01T16:50:03Z
• Authors: Marcos R.H. Estécio; Vazganush Gharibyan; Lanlan Shen; Ashraf E.K. Ibrahim; Ketan Doshi; Rong He; Jaroslav Jelinek; Allen S. Yang; Pearlly S. Yan; Tim H-M. Huang; Eloiza H. Tajara; Jean-Pierre J. Issa
• Keywords: Microsatellite Instability; MLH1; CpG site; Bisulfite sequencing; DNA demethylation

BackgroundAlterations in DNA methylation cancer include global hypomethylation and gene-specific hypermethylation. It is not clear whether these two epigenetic errors are mechanistically linked or occur independently. This study was performed to determine the relationship between hypomethylation, hypermethylation microsatellite instability cancer.Methodology/Principal FindingsWe examined 61 cell lines 60 colorectal carcinomas their adjacent tissues using LINE-1 bisulfite-PCR as a surrogate for demethylation. Colorectal with sporadic (MSI), most of which due CpG island phenotype (CIMP) associated MLH1 promoter methylation, showed average no difference normal tissues. Interestingly, some tumor samples this group increase methylation. In contrast, MSI-showed significant decrease (P<0.001). Microarray analysis repetitive element confirmed observation high degree variability samples. Additionally, unsupervised hierarchical clustering identified highly hypomethylated tumors, composed mostly tumors without instability. We extended from different found that 50/61 were compared peripheral blood lymphocytes colon mucosa. also exhibited large variation demethylation, tissue-specific thus unlikely be resultant stochastic process.Conclusion/SignificanceGlobal partially reversed cancers shows cancer, may reflect alternative progression pathways cancer.