Hypermethylation of RASSF1A in human and rhesus placentas

Rossa W.K. Chiu, Stephen S.C. Chim, Ivy H.N. Wong, Sze Chuen Cesar Wong, Wing Shan Lee, Ka F. To, Joanna H.M. Tong, Ryan K.C. Yuen, Alisa S.W. Shum, John K.C. Chan, Lisa Y.S. Chan, Jessie W.F. Yuen, Yu K. Tong, Jingly F. Weier, Christy Ferlatte, Tse N. Leung, Tze K. Lau, Kwok W. Lo, Y. M.Dennis Lo

Research output: Journal article publicationJournal articleAcademic researchpeer-review

113 Citations (Scopus)

Abstract

The pseudomalignant nature of the placenta prompted us to search for tumor suppressor gene hypermethylation, a phenomenon widely reported in cancer, in the human placenta. Nine tumor suppressor genes were studied. Hypermethylation of the Ras association domain family 1 A (RASSF1A) gene was found in human placentas from all three trimesters of pregnancy but was absent in other fetal tissues. Hypermethylation of Rassf1 was similarly observed in placentas from the rhesus monkey but not the mouse. An inverse relationship between RASSF1A promoter methylation and gene expression was demonstrated by bisulfite sequencing of microdissected placental cells and immunohistochemical staining of placental tissue sections using an anti-RASSF1A antibody. Treatment of choriocarcinoma cell lines, JAR and JEG3, by 5-aza-2′-deoxycytidine and trichostatin A led to reduction in RASSF1A methylation but increased expression. These observations extend the analogy between the primate placenta and malignant tumors to the epigenetic level.
Original languageEnglish
Pages (from-to)941-950
Number of pages10
JournalAmerican Journal of Pathology
Volume170
Issue number3
DOIs
Publication statusPublished - 1 Jan 2007
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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