Evidence map›Paper›PMID 23442791›Full record

ArticleBMC cancer2013

Transposon activation mutagenesis as a screening tool for identifying resistance to cancer therapeutics.

Li Chen, Lynda Stuart, Toshiro K Ohsumi, Shawn Burgess, Gaurav K Varshney, Anahita Dastur, Mark Borowsky, Cyril Benes, Adam Lacy-Hulbert, Emmett V Schmidt

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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

20 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Zebrafish models of acute leukemias: Current models and future directions.Wiley interdisciplinary reviews. Developmental biology · 2021
    Review
  5. Article
  6. Article
  7. Article
  8. Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  9. Review
  10. Downregulation of cytochromeOncology letters · 2017
    Article
  11. Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an ArfProceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Li ChenCenter for Molecular Therapeutics, Center for Cancer Research, Massachusetts General Hospital, and Harvard Medical School, CNY 149-Rm7308, Thirteenth St. Charlestown, MA 02129, USA. lchen13@partners.org
Lynda Stuart
Toshiro K Ohsumi
Shawn Burgess
Gaurav K Varshney
Anahita Dastur
Mark Borowsky
Cyril Benes
Adam Lacy-Hulbert
Emmett V Schmidt
Massachusetts General Hospital · USHarvard University · USNational Human Genome Research Institute · US

Funding

Zebrafish targeted mutagenesis and functional genomicsZIAHG000183 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BURGESS, SHAWN M · 2009 to 2025
$16.7M
Evolutionary lead optimization for immunotherapy of Marburg & Ebola virusesU01AI070330 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LACY-HULBERT, ADAM · 2006 to 2010
$4.4M
Transposon Mutagenesis for Host-Target and Drug Discovery in Infectious DiseaseR21AI102266 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LACY-HULBERT, ADAM, STUART, LYNDA · 2012 to 2013
$464k
NIAID NIH HHS R21 AI102266NIAID NIH HHS U01 AI070330NIAID NIH HHS U01-AI070330Wellcome Trust 086357
6 · The paper itself

Abstract

backgroundThe development of resistance to chemotherapies represents a significant barrier to successful cancer treatment. Resistance mechanisms are complex, can involve diverse and often unexpected cellular processes, and can vary with both the underlying genetic lesion and the origin or type of tumor. For these reasons developing experimental strategies that could be used to understand, identify and predict mechanisms of resistance in different malignant cells would be a major advance.

methodsHere we describe a gain-of-function forward genetic approach for identifying mechanisms of resistance. This approach uses a modified piggyBac transposon to generate libraries of mutagenized cells, each containing transposon insertions that randomly activate nearby gene expression. Genes of interest are identified using next-gen high-throughput sequencing and barcode multiplexing is used to reduce experimental cost.

resultsUsing this approach we successfully identify genes involved in paclitaxel resistance in a variety of cancer cell lines, including the multidrug transporter ABCB1, a previously identified major paclitaxel resistance gene. Analysis of co-occurring transposons integration sites in single cell clone allows for the identification of genes that might act cooperatively to produce drug resistance a level of information not accessible using RNAi or ORF expression screening approaches.

conclusionWe have developed a powerful pipeline to systematically discover drug resistance in mammalian cells in vitro. This cost-effective approach can be readily applied to different cell lines, to identify canonical or context specific resistance mechanisms. Its ability to probe complex genetic context and non-coding genomic elements as well as cooperative resistance events makes it a good complement to RNAi or ORF expression based screens.

Indexed as

Antineoplastic Agents, PhytogenicBlotting, WesternCell Line, TumorDNA Barcoding, TaxonomicDNA Mutational AnalysisDNA Transposable ElementsDrug Resistance, NeoplasmHumansMutagenesis, InsertionalNeoplasmsPaclitaxelRNA, MessengerAntineoplastic Agents, PhytogenicDNA Transposable ElementsPaclitaxelRNA, Messenger

Identifiers

PMID23442791
PMCPMC3598783
OpenAlexW2159226010

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.