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Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts

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Version 2 2024-06-04, 13:34
Version 1 2019-03-01, 11:12
journal contribution
posted on 2024-06-04, 13:34 authored by B Novakovic, V Rakyan, HK Ng, U Manuelpillai, C Dewi, NC Wong, R Morley, T Down, S Beck, Jeffrey CraigJeffrey Craig, R Saffery
Human 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 reproduction

Volume

14

Pagination

547-554

Location

Oxford, Eng.

Open access

  • Yes

ISSN

1360-9947

eISSN

1460-2407

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2008, The Author

Issue

9

Publisher

Oxford University Press