Hypermethylation of RASSF1A in human and rhesus placentas

Am J Pathol. 2007 Mar;170(3):941-50. doi: 10.2353/ajpath.2007.060641.


The pseudomalignant nature of the placenta prompted us to search for tumor suppressor gene hypermethylation, a phenomenon widely reported in cancer, in the human placenta. Nine tumor suppressor genes were studied. Hypermethylation of the Ras association domain family 1 A (RASSF1A) gene was found in human placentas from all three trimesters of pregnancy but was absent in other fetal tissues. Hypermethylation of Rassf1 was similarly observed in placentas from the rhesus monkey but not the mouse. An inverse relationship between RASSF1A promoter methylation and gene expression was demonstrated by bisulfite sequencing of microdissected placental cells and immunohistochemical staining of placental tissue sections using an anti-RASSF1A antibody. Treatment of choriocarcinoma cell lines, JAR and JEG3, by 5-aza-2'-deoxycytidine and trichostatin A led to reduction in RASSF1A methylation but increased expression. These observations extend the analogy between the primate placenta and malignant tumors to the epigenetic level.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • DNA Methylation*
  • DNA Primers
  • Epigenesis, Genetic*
  • Female
  • Gene Expression
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Lasers
  • Macaca mulatta
  • Mice
  • Microdissection
  • Molecular Sequence Data
  • Placenta / physiology*
  • Pregnancy
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Tumor Suppressor Proteins / genetics*


  • Biomarkers, Tumor
  • DNA Primers
  • RASSF1 protein, human
  • Tumor Suppressor Proteins