Epigenetic instability of imprinted genes in human cancers

Many imprinted genes are often epigenetically af-fected in human cancers due to their functional link-age to insulin and insulin-like growth factor signal-ing pathways. Thus, the current study systemati-cally characterized the epigenetic instability of im-printed genes in multiple human cancers. First, the survey results from TCGA (The Cancer Genome At-las) revealed that the expression levels of the major-ity of imprinted genes are downregulated in primary tumors compared to normal cells. These changes are also accompanied by DNA methylation level changes in several imprinted domains, such as the PEG3, MEST and GNAS domains. Second, these DNA methylation level changes were further confirmed manually using several sets of cancer DNA. Accord-ing to the results, the Imprinting Control Regions of the PEG3, MEST and GNAS domains are indeed af-fected in breast, lung and ovarian cancers. This DNA methylation survey also revealed that evolutionarily conserved cis-regulatory elements within these im-printed domains are very variable in both normal and cancer cells. Overall, this study highlights the epige-netic instability of imprinted domains in human can-cers and further suggests its potential use as cancer biomarkers