Do breast cancer cell lines provide a relevant model of the patient tumor methylome?

Leslie M. Cope, Mary Jo Fackler, Zoila Lopez-Bujanda, Antonio C. Wolff, Kala Visvanathan, Joe W. Gray, Saraswati Sukumar, Christopher B. Umbricht

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Article numbere105545
JournalPloS one
Volume9
Issue number8
DOIs
StatePublished - Aug 26 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Cope, L. M., Fackler, M. J., Lopez-Bujanda, Z., Wolff, A. C., Visvanathan, K., Gray, J. W., Sukumar, S., & Umbricht, C. B. (2014). Do breast cancer cell lines provide a relevant model of the patient tumor methylome? PloS one, 9(8), [e105545]. https://doi.org/10.1371/journal.pone.0105545