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Human Molecular Genetics, 2001, Vol. 10, No. 13 1413-1419
© 2001 Oxford University Press

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

Dominic J. Smiraglia1,+, Laura J. Rush1,2, Michael C. Frühwald1,7, Zunyan Dai1,3, William A. Held8, Joseph F. Costello9, James C. Lang4, Charis Eng1,5, Bin Li1, Fred A. Wright1, Michael A. Caligiuri1,6 and Christoph Plass1

1Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, 2Department of Veterinary Biosciences, 3Department of Pathology, 4Department of Otolaryngology, 5Division of Human Genetics and 6Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA, 7Westfälische Wilhelms-Universität Münster, Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie/Onkologie, Münster 48149, Germany, 8Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA and 9Department of Neurological Surgery and the Brain Tumor Research Center, University of California San Francisco, 2340 Sutter Street, Room N261, Box 0875, San Francisco, CA 94143-0875, USA

Cancer cell lines are widely used in many types of cancer research, including studies aimed at understanding DNA hypermethylation of gene promoters in cancer. Hypermethylation of promoters is capable of repressing the expression 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 comparison between them. In order to address this question, we have utilized restriction landmark genomic scanning to measure the hypermethylation phenotypes of cancer cell lines and compared these data with the same analysis performed on primary malignancies. In all cases, cancer cell lines exhibit significantly higher levels of CpG island hypermethylation than the primary malignancies they represent. Colon cancer cell lines are most similar to their respective tumors, with only a 5-fold increase in hypermethylation, while head and neck squamous cell carcinoma cell lines show a 93-fold increase in hypermethylation. Furthermore, >57% of the loci methylated in cell lines are never methylated in 114 primary malignancies studied. Seventy percent of loci hypermethylated in cell lines are hypermethylated in lines from more than one type of cancer. These data indicate that most CpG island hypermethylation observed in cancer cell lines is due to an intrinsic property of cell lines as opposed to the malignant tissue from which they originated.

+ To whom correspondence should be addressed at: The Ohio State University, Department of Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics, 420 West 12th Avenue, Medical Research Facility, Room 470A, Columbus, OH 43210, USA; Tel: +1 614 292 6478; Fax: +1 614 688 4761; Email: Smiraglia.1@postbox.acs.ohio-state.edu


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