title: Do breast cancer cell lines provide a relevant model of the patient tumor methylome?
abstract: It is well documented that tumor cells undergo dramatic genetic and epigenetic changes during initial establishment as cell lines and in subsequent serial passaging, and that the resultant cell lines may have evolved significantly from the primary tumors from which they were derived. This has potential implications due to their widespread use in drug response experiments and studies of genomic function. One approach to optimizing the design of such cell line studies is to identify and use the cell lines that faithfully recapitulate critical features of primary tumors. To evaluate the epigenetic fidelity of breast cancer cell lines in the context of primary tumors, we performed methylation profiling of 55 well-characterized breast cancer cell lines on the Illumina HumanMethylation27 BeadChip platform, and compared them to publicly available methylation profiles of primary breast tumors. We found that the DNA methylation profiles of breast cancer cell lines largely retain the features that characterize primary tumors, although there are crucial differences as well. We describe these similarities and differences between primary tumors and breast cancer cell lines in detail, and develop a quantitative measure of similarity that is used to score each cell line with respect to how faithfully its methylation profile mirrors that of primary tumors.
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Cope
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Fackler
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Zoila
authors.initials: Z
authors.lastname: Lopez-Bujanda
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.affiliation: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Umbricht
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans