Evidence map›Paper›PMID 30089904›Full record

ArticleNature2018

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 and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 563 papers.

0numbers the graph read from it
0cells of the map it votes in
563citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

563 citing papers in PubMed.

  1. A Tissue Explant Model for Colon Cancer.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Animal organoids as models for integrated One Health research.One health (Amsterdam, Netherlands) · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Humoral immunity in cancer.Signal transduction and targeted therapy · 2026
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

503 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Uri Ben-DavidBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Benjamin SiranosianBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Gavin HaBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Helen TangBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Yaara OrenBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Kunihiko HinoharaBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Craig A StrathdeeBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Joshua DempsterBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Nicholas J LyonsBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Robert BurnsDana-Farber Cancer Institute, Boston, MA, USA.
Anwesha NagDana-Farber Cancer Institute, Boston, MA, USA.
Guillaume KugenerBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Beth CiminiBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Peter TsvetkovBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Yosef E MaruvkaBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Ryan O'RourkeBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Anthony GarrityBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Andrew A TubelliBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Pratiti BandopadhayayBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Aviad TsherniakBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Francisca VazquezBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Bang WongBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Chet BirgerBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Mahmoud GhandiBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Aaron R ThornerDana-Farber Cancer Institute, Boston, MA, USA.
Joshua A BittkerBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Matthew MeyersonBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Gad GetzBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Rameen BeroukhimBroad Institute of Harvard and MIT, Cambridge, MA, USA. rameen_beroukhim@dfci.harvard.edu.
Todd R GolubBroad Institute of Harvard and MIT, Cambridge, MA, USA. golub@broadinstitute.org.

Funding

Discovering existing medicines that abrogate cellular responses to SARS CoV-2 infectionU54HL127366 · NHLBI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2014 to 2020
$14.3M
There and Back Again: Epigenetic Reinforcement of Cellular Signaling States - OverallU54HG008097 · NHGRI · BROAD INSTITUTE, INC. · PI JAFFE, JACOB DAVID · 2014 to 2019
$9.3M
Genetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9M
Characterizing TP53 and PPM1D mutations as resistance drivers to radiation therapy in Diffuse Intrinsic Pontine GliomasR01CA219943 · NCI · BROAD INSTITUTE, INC. · PI BEROUKHIM, RAMEEN, LIGON, KEITH LLOYD · 2017 to 2021
$2.5M
NCI NIH HHS R01 CA188228NCI NIH HHS R01 CA219943NHGRI NIH HHS U54 HG008097NHLBI NIH HHS U54 HL127366
6 · The paper itself

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.

Indexed as

Evolution, MolecularBreast NeoplasmsCell ProliferationCell ShapeClone CellsGenetic VariationGenomic InstabilityHumansMCF-7 CellsReproducibility of ResultsTranscription, Genetic

Identifiers

PMID30089904
PMCPMC6522222

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.