craig-specifictumour-2008.pdf (963.43 kB)
Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts
journal contribution
posted on 2008-09-01, 00:00 authored by B Novakovic, V Rakyan, H K Ng, U Manuelpillai, C Dewi, N C Wong, R Morley, T Down, S Beck, Jeffrey CraigJeffrey Craig, R SafferyHuman placentation displays many similarities with tumourigenesis, including rapid cell division, migration and invasion, overlapping gene expression profiles and escape from immune detection. Recent data have identified promoter methylation in the Ras association factor and adenomatous polyposis coli tumour suppressor genes as part of this process. However, the extent of tumour-associated methylation in the placenta remains unclear. Using whole genome methylation data as a starting point, we have examined this phenomenon in placental tissue. We found no evidence for methylation of the majority of common tumour suppressor genes in term placentas, but identified methylation in several genes previously described in some human tumours. Notably, promoter methylation of four independent negative regulators of Wnt signalling has now been identified in human placental tissue and purified trophoblasts. Methylation is present in baboon, but not in mouse placentas. This supports a role for elevated Wnt signalling in primate trophoblast invasiveness and placentation. Examination of invasive choriocarcinoma cell lines revealed altered methylation patterns consistent with a role of methylation change in gestational trophoblastic disease. This distinct pattern of tumour-associated methylation implicates a coordinated series of epigenetic silencing events, similar to those associated with some tumours, in the distinct features of normal human placental invasion and function.
History
Journal
Molecular human reproductionVolume
14Issue
9Pagination
547 - 554Publisher
Oxford University PressLocation
Oxford, Eng.Publisher DOI
ISSN
1360-9947eISSN
1460-2407Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2008, The AuthorUsage metrics
Keywords
AnimalsBasic Helix-Loop-Helix Transcription FactorsCarrier ProteinsCell Line, TumorCells, CulturedDNA MethylationEarly Growth Response Transcription FactorsFemaleHumansHyaluronan ReceptorsIn Vitro TechniquesMembrane ProteinsMiceNeoplasmsPapioPlacentaPregnancyPregnancy Trimester, FirstRepressor ProteinsTrophoblastsTumor Suppressor ProteinsWnt signallingchoriocarcinomaScience & TechnologyLife Sciences & BiomedicineDevelopmental BiologyObstetrics & GynecologyReproductive BiologycytotrophoblastsACUTE LYMPHOBLASTIC-LEUKEMIAGENOME-WIDE ANALYSISEPIGENETIC REGULATIONPROMOTER METHYLATIONGENE-EXPRESSIONTRANSCRIPTIONAL ACTIVITYCOLORECTAL-CANCERSIGNALING PATHWAYDOWN-REGULATIONPhysiology
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC