Identification of DNA methylation markers for detection and classification of colon cancer

Judith Boer, Tom van Wezel and Hans Morreau

Epigenetic modification of gene expression by aberrant methylation of promoter CpG islands plays an important role in the initiation and development of colorectal cancer (CRC). Since aberrant methylation is thought to be one of the earliest steps in tumorigenesis detection of methylation-based markers is very attractive. In addition, the stability of methylation changes in the DNA allows the development of cost-effective and sensitive assays.

Therefore, we aim at the identification of high-performance DNA methylation markers for the detection and classification of CRC and its precursor forms. We are carrying out genome-wide methylation studies in a consecutive series of clinically well-described colon tumors and paired normal samples using differential methylation hybridization of CpG island microarrays. This assay will hopefully provide differentially methylated loci which will be verified on the levels of methylation and expression. Verified loci can be used as methylation markers in future diagnostic tests.

Another aim in this study is to classify possible genetic factors contributing to the observed increase of differential methylation in colon cancer. A subset of young sporadic MSI-H colon cancer patients with MLH1 methylation are investigated to search for possible causative genomic factors in this disease associated with aberrant epigenetics.

References

- van Roon,E.H., de Miranda,N.F., van Nieuwenhuizen,M.P., de Meijer,E.J., van Puijenbroek,M., Yan,P.S., Huang,T.H., van Wezel,T., Morreau,H., and Boer,J.M. (2010a). Tumour-specific methylation of PTPRG intron 1 locus in sporadic and Lynch syndrome colorectal cancer. Eur. J. Hum. Genet. 19, 307-312.


- van Roon,E.H., van Puijenbroek,M., Middeldorp,A., van Eijk,R., de Meijer,E.J., Erasmus,D., Wouters,K.A., van Engeland,M., Oosting,J., Hes,F.J., Tops,C.M., van Wezel,T., Boer,J.M., and Morreau,H. (2010b). Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition? BMC. Cancer 10, 180.