RT Journal Article SR Electronic T1 Demethylation of the Region around Exon 2 of MLH1 Gene in Gastrointestinal Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4861 OP 4864 VO 32 IS 11 A1 YANPING TANG A1 CONG LIU A1 XIYIN WANG A1 DONG LIU A1 SIGURDUR INGVARSSON A1 HUIPING CHEN YR 2012 UL http://ar.iiarjournals.org/content/32/11/4861.abstract AB Aim: Our previous study showed that methylation of the mutL homolog 1 (MLH1) promoter may spread upstream from the Alu elements in intron 1. In this study, we investigated if the Alu methylation could also spread downstream. Materials and Methods: Two colorectal cancer cell lines (RKO, SW48), and four colorectal and three gastric carcinomas [all Microsatellite Instability (MSI)-positive] were selected as cases. Normal colorectal and gastric mucosa and human peripheral blood, and one MSI-negative colorectal cancer case served as controls. After extraction of DNA, bisulfite genomic sequencing was used to analyze the methylation level of exon 2 and the adjacent part of intron 2 of the MLH1 gene. Results: Exon 2 and the partial intron 2 exhibited a high level of methylation in controls. In contrast, demethylation in these regions was seen in gastrointestinal cancer. Conclusion: Exon 2 methylation is not likely to influence MLH1 gene expression. It seems that de-methylation of exon 2 and intron 2, in combination with intron 1, is associated with methylation spreading of the MLH1 promoter. The region around exon 2 could possibly bind proteins that regulate methylation, and therefore affect gene expression.