title: Promoter methylation in head and neck squamous cell carcinoma cell lines is significantly different than methylation in primary tumors and xenografts.
abstract: Studies designed to identify novel methylation events related to cancer often employ cancer cell lines in the discovery phase of the experiments and have a relatively low rate of discovery of cancer-related methylation events. An alternative algorithm for discovery of novel methylation in cancer uses primary tumor-derived xenografts instead of cell lines as the primary source of nucleic acid for evaluation. We evaluated DNA extracted from primary head and neck squamous cell carcinomas (HNSCC), xenografts grown from these primary tumors in nude mice, HNSCC-derived cell lines, normal oral mucosal samples, and minimally transformed oral keratinocyte-derived cell lines using Illumina Infinum Humanmethylation 27 genome-wide methylation microarrays. We found >2,200 statistically significant methylation differences between cancer cell lines and primary tumors and when comparing normal oral mucosa to keratinocyte cell lines. We found no statistically significant promoter methylation differences between primary tumor xenografts and primary tumors. This study demonstrates that tumor-derived xenografts are highly accurate representations of promoter methylation in primary tumors and that cancer derived cell lines have significant drawbacks for discovery of promoter methylation alterations in primary tumors. These findings also support use of primary tumor xenografts for the study of methylation in cancer, drug discovery, and the development of personalized cancer treatments.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Hennessey
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ochs
authors.forename: Wojciech W
authors.initials: WW
authors.lastname: Mydlarz
authors.forename: Wayne
authors.initials: W
authors.lastname: Hsueh
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015342:DNA Probes / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013447:Sulfites / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D015342:DNA Probes; D013447:Sulfites; C042345:hydrogen sulfite