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 language | English |
|---|---|
| Pages (from-to) | 56-62 |
| Number of pages | 7 |
| Journal | Cancer Letters |
| Volume | 268 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 8 Sep 2008 |
| Externally published | Yes |
Keywords
- Adenamatous polyposis coli
- Epigenetics
- Methylation
- Placenta
- Tumour suppressor
Cite this
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Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells. / Wong, N. C.; Novakovic, B.; Weinrich, B.; Dewi, C.; Andronikos, R.; Sibson, M.; Macrae, F.; Morley, R.; Pertile, M. D.; Craig, J. M.; Saffery, R.
In: Cancer Letters, Vol. 268, No. 1, 08.09.2008, p. 56-62.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells
AU - Wong, N. C.
AU - Novakovic, B.
AU - Weinrich, B.
AU - Dewi, C.
AU - Andronikos, R.
AU - Sibson, M.
AU - Macrae, F.
AU - Morley, R.
AU - Pertile, M. D.
AU - Craig, J. M.
AU - Saffery, R.
PY - 2008/9/8
Y1 - 2008/9/8
N2 - 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.
AB - 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.
KW - Adenamatous polyposis coli
KW - Epigenetics
KW - Methylation
KW - Placenta
KW - Tumour suppressor
UR - http://www.scopus.com/inward/record.url?scp=48149114291&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2008.03.033
DO - 10.1016/j.canlet.2008.03.033
M3 - Article
VL - 268
SP - 56
EP - 62
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -