Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas
Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas
Blog Article
Abstract Background The methylation of the CpG islands of the LINE-1 promoter is a tight control mechanism on the function of mobile elements.However, simultaneous quantification of promoter methylation and transcription of LINE-1 has not been performed in progressive stages of colorectal cancer.In addition, the insertion of mobile elements in the genome Tape of advanced adenoma stage, a precancerous stage before colorectal carcinoma has not been emphasized.In this study, we quantify promoter methylation and transcripts of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma.
In addition, we analyze the insertion of LINE-1, Alu, and SVA elements in the genome of patient tumors with colorectal advanced adenomas.Methods LINE-1 hypomethylation status was evaluated by absolute quantitative analysis of methylated alleles (AQAMA) assay.To quantify the level of transcripts for LINE-1, quantitative RT-PCR was performed.To find mobile element insertions, the advanced adenoma tissue samples were subjected to whole genome sequencing and MELT analysis.
Results We found that the LINE-1 promoter methylation in advanced adenoma and adenocarcinoma was significantly lower than that in non-advanced adenomas.Accordingly, the copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas.Whole-genome sequencing analysis of colorectal advanced adenomas revealed that at this stage polymorphic insertions of LINE-1, Alu, and SVA comprise approximately 16%, 51%, and 74% of total insertions, respectively.Conclusions Our correlative analysis showing a decreased methylation 137 of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and polymorphic genomic insertions in advanced adenoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.