title: Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells.
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.
authors.affiliation: Epigenetics Research, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria 3052, Australia.
authors.forename: N C
authors.initials: NC
authors.lastname: Wong
authors.forename: B
authors.initials: B
authors.lastname: Novakovic
authors.forename: B
authors.initials: B
authors.lastname: Weinrich
authors.forename: C
authors.initials: C
authors.lastname: Dewi
authors.forename: R
authors.initials: R
authors.lastname: Andronikos
authors.forename: M
authors.initials: M
authors.lastname: Sibson
authors.forename: F
authors.initials: F
authors.lastname: Macrae
authors.forename: R
authors.initials: R
authors.lastname: Morley
authors.forename: M D
authors.initials: MD
authors.lastname: Pertile
authors.forename: J M
authors.initials: JM
authors.lastname: Craig
authors.forename: R
authors.initials: R
authors.lastname: Saffery
mesh_terms: D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D017491:Genes, APC; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011401:Promoter Regions, Genetic