Specific hypomethylated CpGs at the IGF2 locus act as an epigenetic biomarker for familial adenomatous polyposis colorectal cancer
2010
Miroglio, Audrey | Jammes, Hélène | Tost, Jorg | Ponger, Loïc | Glynne Gut, Ivo | El Abdalaoui, Hafida | Coste, Joël | Chaussade, Stanislas | Arimondo, P. B | Lamarque, Dominique | Dandolo, Luisa
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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