Table 1.

Key epigenetic similarities between the placenta and human cancer.

Feature	Detail
Global hypomethylation	Placental tissue and human cancers show a global 5-methylcytosine content of ~3%, lower than that of all disease-free somatic tissues (4–5%). This is associated with a loss of methylation at specific repeat sequences (mainly LINE1) that comprise the bulk (~50%) of genomic DNA and long genomic regions of intermediate methylation, called partially methylated domains (PMDs), which cover 37% of the placental genome. The presence of PMDs is a feature of most human cancers.	Gama-Sosa etal. (1983), Tabano etal. (2010), and Schroeder etal. (2013)
Tumor suppressor gene (TSG) methylation	RASSF1A is hypermethylated in almost every cancer type and was the first TSG shown to be specifically methylated in the placenta. Methylation of multiple negative regulators of Wnt signaling (APC, WIF-1, SFRP2, EN1) demonstrates coordinated epigenetic regulation of signaling pathways in placenta and cancer. Multiple examples of monoallelic methylation indicate a potential suite of novel imprinted genes involved in the regulation of placentation in humans.	Chiu etal. (2007), Novakovic etal. (2008), Wong etal. (2008), and Guilleret etal. (2009)
Loss of imprinting (LOI)	Imprinting (parent of origin allele specific expression) is regulated by DNA methylation. LOI common in placenta, and is one of the most consistent epigenetic aberrations observed in cancer.	Lambertini etal. (2008a) and Diplas etal. (2009b)
Cryptic promoter/enhancer activation	Global hypomethylation results in placenta-specific activation of transposable elements to produce novel promoter and enhancer elements. This leads to generation of placenta-specific transcripts of endogenous genes. Additionally, several retrotransposable elements are exclusively expressed in the placenta and cancer and are essential for faithful placentation.	Macaulay etal. (2011) and Vargas etal. (2012)
miRNAs	Some miRNA genes, including the large microRNA cluster C19MC, are expressed only in the placenta and in human cancers in association with hypomethylation of an upstream CpG islands. Altered miRNA expression leads to placental/cancer specific changes in downstream gene expression of target loci.	Bortolin-Cavaille etal. (2009)