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BMC Medical Genomics

, 4:82

Functional and structural genomics

Abstract

BackgroundEpigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.

MethodsWe profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique methylated CpG island recovery assay in combination with a genome analyzer and a new normalization algorithm.

ResultsWe were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands CGIs, transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5- CGIs and the 5-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5- CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing LRES regions in gastric cancer tissue and identified several hypermethylated genes MDM2, DYRK2, and LYZ within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.

ConclusionsOur findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-4-82 contains supplementary material, which is available to authorized users.

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Author: Jung-Hoon Park - Jinah Park - Jung Kyoon Choi - Jaemyun Lyu - Min-Gyun Bae - Young-Gun Lee - Jae-Bum Bae - Dong Yoon Par

Source: https://link.springer.com/



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