Epigenetic instability of imprinted genes in human cancers.
Many imprinted genes are often epigenetically affected in human cancers due to their functional linkage to insulin and insulin-like growth factor signaling pathways. Thus, the current study systematically characterized the epigenetic instability of imprinted genes in multiple human cancers. First, the survey results from TCGA (The Cancer Genome Atlas) revealed that the expression levels of the majority 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. According to the results, the Imprinting Control Regions of the PEG3, MEST and GNAS domains are indeed affected in breast, lung and ovarian cancers. This DNA methylation survey also revealed that evolutionarily conserved cis-regulatory elements within these imprinted domains are very variable in both normal and cancer cells. Overall, this study highlights the epigenetic instability of imprinted domains in human cancers and further suggests its potential use as cancer biomarkers.
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA jkim@lsu.edu.
Joomyeong
J
Kim
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Corey L
CL
Bretz
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Suman
S
Lee
D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional