1. ¹Unité INSERM 590, Laboratoire d'Oncologie Moléculaire, Centre Léon Bérard, Lyon Cedex, France
2. ²Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Madrid, Spain
3. ³Laboratoire d'Anatomie Pathologie, Hôpital Edouard Herriot, Lyon, France
4. ⁴Laboratoire de Biologie de la Reproduction et du Développement, UCBL1, Lyon Cedex, France

Correspondence: Dr R Dante, Unité INSERM 590, Laboratoire d'Oncologie Moléculaire, Centre Léon Bérard, 28 rue Laennec, Rhone, 69373 Lyon Cedex 08, France. E-mail: dante@univ-lyon1.fr

Received 28 June 2006; Revised 10 August 2006; Accepted 14 August 2006; Published online 9 October 2006.

Abstract

In human post-natal somatic cells, low global levels of DNA methylation have been associated with the hypomethylation of several repetitive elements, a feature that has been proposed to be a surrogate epigenetic marker. These data, mainly derived from the analysis of cancer cells, suggest a potential association between loss of cell-growth control and altered differentiation with hypomethylation of repetitive sequences. Partial hydatidiform moles (PHMs) can be used as an alternative model for investigating this association in a non-tumorigenic context. This gestational disease is characterized by abnormal overgrowth and differentiation of the placenta and spontaneous abortion. Here, we comprehensively analyse the DNA methylation of these trophoblastic tissues in both PHM and normal placenta at global and sequence-specific levels. Analysis of the global 5-methylcytosine content and immunohistochemistry indicate that PHM and normal placenta have identical global levels of DNA methylation. In contrast, bisulfite genomic sequencing shows that, whereas Alu, NBL2 and satellite 2 repetitive elements are equally methylated, LINE-1 sequences are hypermethylated in PHM tissues (2-fold relative to normal placenta). Interestingly, altered demethylation is also found in triploid diandric embryos that originate from dispermic fertilization of an oocyte, a common event responsible for most PHMs. In conclusion, alterations of DNA methylation do not seem to be randomly distributed in PHM, as several repeated elements remain unaltered, whereas LINE-1 sequences are hypermethylated. In addition, our findings suggest that the hypomethylation of repetitive elements in cancer is directly linked to the neoplasic process and not a simple consequence of loss of growth control observed in most of the cancer cells.