Genetic and transcriptional evolution alters cancer cell line drug response

Uri Ben-David, Benjamin Siranosian, Gavin Ha, Helen Tang, Yaara Oren, Kunihiko Hinohara, Craig A. Strathdee, Joshua Dempster, Nicholas J. Lyons, Robert Burns, Anwesha Nag, Guillaume Kugener, Beth Cimini, Peter Tsvetkov, Yosef E. Maruvka, Ryan O’Rourke, Anthony Garrity, Andrew A. Tubelli, Pratiti Bandopadhayay, Aviad Tsherniak, Francisca Vazquez, Bang Wong, Chet Birger, Mahmoud Ghandi, Aaron R. Thorner, Joshua A. Bittker, Matthew Meyerson, Gad Getz, Rameen Beroukhim () and Todd R. Golub ()
Additional contact information
Uri Ben-David: Broad Institute of Harvard and MIT
Benjamin Siranosian: Broad Institute of Harvard and MIT
Gavin Ha: Broad Institute of Harvard and MIT
Helen Tang: Broad Institute of Harvard and MIT
Yaara Oren: Broad Institute of Harvard and MIT
Kunihiko Hinohara: Broad Institute of Harvard and MIT
Craig A. Strathdee: Broad Institute of Harvard and MIT
Joshua Dempster: Broad Institute of Harvard and MIT
Nicholas J. Lyons: Broad Institute of Harvard and MIT
Robert Burns: Dana-Farber Cancer Institute
Anwesha Nag: Dana-Farber Cancer Institute
Guillaume Kugener: Broad Institute of Harvard and MIT
Beth Cimini: Broad Institute of Harvard and MIT
Peter Tsvetkov: Broad Institute of Harvard and MIT
Yosef E. Maruvka: Broad Institute of Harvard and MIT
Ryan O’Rourke: Broad Institute of Harvard and MIT
Anthony Garrity: Broad Institute of Harvard and MIT
Andrew A. Tubelli: Broad Institute of Harvard and MIT
Pratiti Bandopadhayay: Broad Institute of Harvard and MIT
Aviad Tsherniak: Broad Institute of Harvard and MIT
Francisca Vazquez: Broad Institute of Harvard and MIT
Bang Wong: Broad Institute of Harvard and MIT
Chet Birger: Broad Institute of Harvard and MIT
Mahmoud Ghandi: Broad Institute of Harvard and MIT
Aaron R. Thorner: Dana-Farber Cancer Institute
Joshua A. Bittker: Broad Institute of Harvard and MIT
Matthew Meyerson: Broad Institute of Harvard and MIT
Gad Getz: Broad Institute of Harvard and MIT
Rameen Beroukhim: Broad Institute of Harvard and MIT
Todd R. Golub: Broad Institute of Harvard and MIT

Nature, 2018, vol. 560, issue 7718, 325-330

Abstract: Abstract Human cancer cell lines are the workhorse of cancer research. Although cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here we use genomic analyses of 106 human cell lines grown in two laboratories to show extensive clonal diversity. Further comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Notably, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single-cell-derived clones demonstrated that continuous instability quickly translates into heterogeneity of the cell line. When the 27 MCF7 strains were tested against 321 anti-cancer compounds, we uncovered considerably different drug responses: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origins and consequences of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (9)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0409-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:560:y:2018:i:7718:d:10.1038_s41586-018-0409-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0409-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().