Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells

N. C. Wong, B. Novakovic, B. Weinrich, C. Dewi, R. Andronikos, M. Sibson, F. Macrae, R. Morley, M. D. Pertile, J. M. Craig, R. Saffery

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

Abstract

Methylation of the human APC gene promoter is associated with several different types of cancers and has also been documented in some pre-cancerous tissues. We have examined the methylation of APC gene promoters in human placenta and choriocarcinoma cells. This revealed a general hypomethylation of the APC-1b promoter and a pattern with monoallelic methylation of the APC-1a promoter in full term placental tissue. However, there was no evidence of a parent-of-origin effect, suggesting random post zygotic origin of methylation. Increased methylation of this promoter was observed in all choriocarcinoma-derived trophoblast cell lines, suggesting a trophoblastic origin of placental APC methylation and implicating APC hypermethylation in the development of this group of gestational tumours. Our demonstration of placental methylation of the APC-1a promoter represents the first observation of monoallelic methylation of this gene in early development, and provides further support for a role of canonical Wnt signalling in placental trophoblast invasiveness. This also implicates tumour suppressor gene silencing as an integral part of normal human placental development.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalCancer Letters
Volume268
Issue number1
DOIs
Publication statusPublished - 8 Sep 2008
Externally publishedYes

Keywords

  • Adenamatous polyposis coli
  • Epigenetics
  • Methylation
  • Placenta
  • Tumour suppressor

Cite this