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The highly repetitive Alu retroelements are regarded as methylation centres in the genome. Methylation in the gene promoters could be spreading from them. Promoter methylation of  MLH1  is frequently detected in cancers, but the underlying mechanism is unclear. The aim of this study is to understand whether the methylation in the Alu elements is associated with promoter methylation in the MLH1 gene. Bisulfite genomic sequencing was used to analyse the CpG sites of the 5′ end (promoter, exon 1 and Alu-containing intron 1) of the  MLH1  gene in colorectal cancer cells and tissues, and gastric cancer tissues. Hypomethylation in the Alu elements and hypermethylation in the promoters and the regions between the promoters and the Alu elements were detected in two cancer cell lines and seven cancer tissues. However, demethylation or hypomethylation of the MLH1 promoter and regions between promoter and the Alu elements, and hypermethylation in the Alu elements, were identified in the normal tissues.  MLH1  promoter methylation may spread from Alu elements that are located in intron 1 of the  MLH1  gene. The  trans-acting  elements binding to the mutation sites could play a role in the methylation spreading.

Spreading of Alu Methylation to the Promoter of the MLH1 Gene in Gastrointestinal Cancer