Abstracts (poster) - Wissenschaft Online

Isabelle GUILLERET, Maria-Chiara OSTERHELD, Richard BRAUNSCHWEIG, Véronique
GASTINEAU, Suzanne TAILLENS
Imprinting of tumor-suppressor genes in human placenta.
Transcriptional deregulation in cancer has been shown to be associated with epigenetic
alterations, in particular in tumor-suppressor-gene (TSG) promoters. In contrast, DNA
methylation in TSG is absent in normal differentiated cells. Nevertheless, we previously
showed that the promoter of the tumor-suppressor gene APC was methylated on one
allele only, in normal gastric cells (1). Recently, RASSF1A has been shown to be
imprinted in normal human placenta (2). To clarify putative TSG methylation in normal
tissues, 23 placenta at the first trimester, on both decidua and villi, and 4 normal nongestational
endometrium were screened for DNA methylation by methylation-sensitive
single-strand conformation analysis (MS-SSCA) and sequencing after bisulfite
modification, on a panel of 12 genes known to be implicated in carcinogenesis. In all
placental villi, 4 promoter TSG genes - APC, SFRP2, RASSF1A and WIF1 - were
hypermethylated, whereas all decidua and normal endometrium did not show any
methylation. Allele-specific methylation analysis revealed that this methylation was
monoallelic. Furthermore, the comparison with maternal DNA indicated that APC and
WIF1 were methylated on the maternal allele, whereas SFRP2 was found methylated on
the paternal allele. Imprinting status of these 4 genes is conserved during pregnancy.
Sequence analysis of WIF1 mRNA revealed that only the unmethylated paternal allele
was transcribed. These results indicate that TSG imprinting is pre-existent in normal
human placenta and should not be confused with carcinogenesis or pathology-induced
methylation.
Literature
1. Clément G, Bosman FT, Fontolliet C, Benhattar J. Monoallelic methylation of the APC
promoter is altered in normal gastric mucosa associated with neoplastic lesions. Cancer
Res. 2004, 64(19):6867-73.
2. Chiu RW, Chim SS, Wong IH, Wong CS, Lee WS, To KF, Tong JH, Yuen RK, Shum AS,
Chan JK, Chan LY, Yuen JW, Tong YK, Weier JF, Ferlatte C, Leung TN, Lau TK, Lo KW, Lo
YM. Hypermethylation of RASSF1A in human and rhesus placentas. Am J Pathol. 2007,
170(3):941-50.
contact:
Dr. Isabelle GUILLERET
University of Lausanne - CHUV
University Institute of Pathology - CHUV
isabelle.guilleret@chuv.ch
Rue du Bugnon 25
1011 Lausanne (Switzerland)