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

Novakovic, B, Rakyan, V, Ng, HK, Manuelpillai, U, Dewi, C, Wong, NC, Morley, R, Down, T, Beck, S, Craig, Jeffrey M and Saffery, R 2008, Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts, Molecular human reproduction, vol. 14, no. 9, pp. 547-554, doi: 10.1093/molehr/gan046.

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Title Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts
Author(s) Novakovic, B
Rakyan, V
Ng, HK
Manuelpillai, U
Dewi, C
Wong, NC
Morley, R
Down, T
Beck, S
Craig, Jeffrey MORCID iD for Craig, Jeffrey M orcid.org/0000-0003-3979-7849
Saffery, R
Journal name Molecular human reproduction
Volume number 14
Issue number 9
Start page 547
End page 554
Total pages 8
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2008-09
ISSN 1360-9947
Keyword(s) Animals
Basic Helix-Loop-Helix Transcription Factors
Carrier Proteins
Cell Line, Tumor
Cells, Cultured
DNA Methylation
Early Growth Response Transcription Factors
Hyaluronan Receptors
In Vitro Techniques
Membrane Proteins
Pregnancy Trimester, First
Repressor Proteins
Tumor Suppressor Proteins
Wnt signalling
Science & Technology
Life Sciences & Biomedicine
Developmental Biology
Obstetrics & Gynecology
Reproductive Biology
Summary 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.
Language eng
DOI 10.1093/molehr/gan046
Field of Research 1114 Paediatrics And Reproductive Medicine
0606 Physiology
1103 Clinical Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, The Author
Persistent URL http://hdl.handle.net/10536/DRO/DU:30119184

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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