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Epigenetic instability of imprinted genes in human cancers
#MMPMID26338779
Kim J
; Bretz CL
; Lee S
Nucleic Acids Res
2015[Dec]; 43
(22
): 10689-99
PMID26338779
show ga
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.
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