Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies

Cancer cell lines are widely used in many types of cancer research, includi ng studies aimed at understanding DNA hypermethylation of gene promoters in cancer. Hypermethylation of promoters is capable of repressing the express ion of tumor suppressor genes and may play a role in the development and/or progression of cancer. Although both primary malignancies and cancer cell lines exhibit this epigenetic phenomenon, there has been no direct comparis on between them. In order to address this question, we have utilized restri ction landmark genomic scanning to measure the hypermethylation phenotypes of cancer cell lines and compared these data with the same analysis perform ed on primary malignancies. In all cases, cancer cell lines exhibit signifi cantly higher levels of CpG island hypermethylation than the primary malign ancies they represent. Colon cancer cell lines are most similar to their re spective tumors, with only a ii-fold increase in hypermethylation, while he ad and neck squamous cell carcinoma cell lines show a 93-fold increase in h ypermethylation. Furthermore, >57% of the loci methylated in cell lines are never methylated in 114 primary malignancies studied. Seventy percent of l oci hypermethylated in cell lines are hypermethylated in lines from more th an one type of cancer. These data indicate that most CPG island hypermethyl ation observed in cancer cell lines is due to an intrinsic property of cell lines as opposed to the malignant tissue from which they originated.