Research Article

Specific hypomethylated CpGs at the IGF2 locus act as an epigenetic biomarker for familial adenomatous polyposis colorectal cancer

Department of Genetics & Development, Institut Cochin, 24, rue Fbg St Jacques, Inserm U567, CNRS UMR 8104, University Paris Descartes, Paris, France

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Hélène Jammes

Biology of Development & Reproduction, INRA – ENVA, Jouy en Josas, France

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Jörg Tost

Laboratory for Epigenetics, CEA-Institut de Génomique, Centre National de Génotypage, Evry, France

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Loïc Ponger

Genome Regulation & Dynamics, Muséum National d’Histoire Naturelle, Paris, France

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Ivo Glynne Gut

Laboratory for Epigenetics, CEA-Institut de Génomique, Centre National de Génotypage, Evry, France

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Hafida El Abdalaoui

Laboratory for Epigenetics, CEA-Institut de Génomique, Centre National de Génotypage, Evry, France

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Joël Coste

Service de Biostatistique, Hôpital Cochin-Saint Vincent de Paul, Paris, France

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Stanislas Chaussade

Unité d’Hépato-Gastroentérologie, Hôpital Cochin-Saint Vincent de Paul, Paris, France

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Paola B Arimondo

Genome Regulation & Dynamics, Muséum National d’Histoire Naturelle, Paris, France

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Dominique Lamarque^*

Unité d’Hépato-Gastroentérologie, Hôpital Hôtel-Dieu, Paris, France

^*These authors contributed equally to this work

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Luisa Dandolo^*

† Author for correspondence

^*These authors contributed equally to this work

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Email the corresponding author at luisa.dandolo@inserm.fr

Published Online:2 Jun 2010https://doi.org/10.2217/epi.10.24

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Abstract

Aims: The identification of specific biomarkers for colorectal cancer is of primary importance for early diagnosis. The aim of this study was to evaluate if methylation changes at the IGF2/H19 locus could be predictive for individuals at high risk for developing sporadic or hereditary colorectal cancer. Materials & methods: Quantitative methylation analysis using pyrosequencing was performed on three differentially methylated regions (DMRs): IGF2 DMR0 and DMR2 and the H19 DMR in DNA samples from sporadic colorectal cancer (n = 26), familial adenomatous polyposis (n = 35) and hereditary nonpolyposis colorectal cancer (n = 19) patients. Results: We report in this article for the first time, that in sporadic colorectal cancer tumor DNA both the IGF2 DMR0 and DMR2 are hypomethylated, while the H19 DMR retains its monoallelic methylation pattern. In lymphocyte DNA, a striking hypomethylation of nine contiguous correlated CpGs was found in the IGF2 DMR2 but only in familial adenomatous polyposis patients. Conclusion: Methylation alterations at the IGF2 locus are more extensive than previously reported and DMR2 hypomethylation in lymphocyte DNA might be a specific epigenetic biomarker for familial adenomatous polyposis patients.

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Acknowledgements

The authors would like to thank Dr S Grandjouan, Professor B Terris (Hôpital Cochin) and Professor A Martin (Hôpital Avicennes, Paris, France) for providing familial adenomatous polyposis and sporadic colorectal cancer patient tissue samples. We are also grateful to members of the Genomic Imprinting Group (Institut Cochin, Paris, France) for helpful discussion, and to A Murrell (Cambridge Research Institute, UK) for helpful comments on the manuscript.

Financial & competing interests disclosure

This study was partly supported by grants from AstraZeneca Irmad, Société Nationale Française de Gastro-Entérologie (SNFGE), the Association pour la Recherche contre le Cancer, the Ligue contre le Cancer, the INSERM and ANR JCJC n°06_134774. Audrey Miroglio was a recipient of an ARC fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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