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Reproductive Sciences
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Hypermethylation of SOX2 Gene in Hydatidiform Mole and Choriocarcinoma

Albert S.M. Li, MMedSc

Department of Pathology, Queen Mary Hospital, University of Hong Kong

Michelle K.Y. Siu, PhD

Department of Pathology, Queen Mary Hospital, University of Hong Kong

HuiJuan Zhang, MD

Department of Pathology, Queen Mary Hospital, University of Hong Kong

Esther S.Y. Wong, BSc

Department of Pathology, Queen Mary Hospital, University of Hong Kong

Kelvin Y.K. Chan, PhD

Department of Pathology, Queen Mary Hospital, University of Hong Kong

Hextan Y.S. Ngan, MD

Department of Obstetrics and Gynaecology the University of Hong Kong, Hong Kong, China

Annie N.Y. Cheung, MD

Department of Pathology, University of Hong Kong, Pokfulam Road, Hong Kong, China, anycheun{at}hkucc.hku.hk

This study investigated the expression and methylation profiles of SOX2, a stem cell—related transcription factor, in placentas and gestational trophoblastic disease. The methylation status of SOX2 promoter region in 55 hydatidiform moles, 4 choriocarcinoma, 23 first trimester, and 15 term placentas was evaluated by methylation-specific polymerase chain reaction. The methylated allele was found in 4.4% (1/23) of first trimester placentas, 26.7% (4/15) term placentas, and 56.4% (31/55) of hydatidiform moles and all choriocarcinoma samples and cell lines. A significant reduction in SOX2 messenger RNA expression was found in the hydatidiform moles (P = .027) when compared with that in the placentas. SOX2 messenger RNA expression was significantly correlated with SOX2 hypermethylation (P < .001). SOX2 expression was restored in choriocarcinoma cell lines following treatment to 5-Aza-2'-deoxycytidine and/or Trichostatin A, demethylation and histone deacetylase inhibitors, respectively, and the response was synergistic. Epigenetic mechanisms may play important role on the transcriptional regulation of SOX2 and contribute to pathogenesis of gestational trophoblastic disease.

Key Words: SOX2 • methylation • placenta • hydatidiform mole • choriocarcinoma.

Reproductive Sciences, Vol. 15, No. 7, 735-744 (2008)
DOI: 10.1177/1933719108322433
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