Evidence map›Paper›PMID 21436051›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis.

Timothy K Starr, Patricia M Scott, Benjamin M Marsh, Lei Zhao, Bich L N Than, M Gerard O'Sullivan, Aaron L Sarver, Adam J Dupuy, David A Largaespada, Robert T Cormier

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

47 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. APOBEC3A catalyzes mutation and drives carcinogenesis in vivo.The Journal of experimental medicine · 2020
    Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Ex Vivo Transposon-Mediated Genetic Screens for Cancer Gene Discovery.Methods in molecular biology (Clifton, N.J.) · 2019
    Article
  18. Article
  19. Article
  20. Article
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 2 countries.

Timothy K StarrDepartment of Genetics, Cell Biology and Development, Center for Genome Engineering, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. star0044@umn.edu
Patricia M Scott
Benjamin M Marsh
Lei Zhao
Bich L N Than
M Gerard O'Sullivan
Aaron L Sarver
Adam J Dupuy
David A Largaespada
Robert T Cormier
University of Minnesota, Duluth · USUniversity of Minnesota · USUniversity of Iowa · US

Funding

TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
Sleeping Beauty for uncovering cancer genes in miceR01CA113636 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW · 2006 to 2016
$2.5M
Transposon-based screens for colorectal cancer genesR01CA134759 · NCI · UNIVERSITY OF MINNESOTA · PI CORMIER, ROBERT T, LARGAESPADA, DAVID ANDREW · 2009 to 2013
$1.5M
Cancer gene discovery using Sleeping Beauty transposon-mediated mutagenesisK99CA151672 · NCI · UNIVERSITY OF MINNESOTA · PI STARR, TIMOTHY KAEHLER · 2010 to 2010
$102k
NCI NIH HHS 1K99CA151672-01NCI NIH HHS K99 CA151672NCI NIH HHS R01 CA113636NCI NIH HHS R01CA113636-01A1NCI NIH HHS R01 CA134759NCI NIH HHS R01 CA134759-01A1NCI NIH HHS T32 CA009138
6 · The paper itself

Abstract

It is proposed that a progressive series of mutations and epigenetic events leads to human colorectal cancer (CRC) and metastasis. Furthermore, data from resequencing of the coding regions of human CRC suggests that a relatively large number of mutations occur in individual human CRC, most at low frequency. The functional role of these low-frequency mutations in CRC, and specifically how they may cooperate with high-frequency mutations, is not well understood. One of the most common rate-limiting mutations in human CRC occurs in the adenomatous polyposis coli (APC) gene. To identify mutations that cooperate with mutant APC, we performed a forward genetic screen in mice carrying a mutant allele of Apc (Apc(Min)) using Sleeping Beauty (SB) transposon-mediated mutagenesis. Apc(Min) SB-mutagenized mice developed three times as many polyps as mice with the Apc(Min) allele alone. Analysis of transposon common insertion sites (CIS) identified the Apc locus as a major target of SB-induced mutagenesis, suggesting that SB insertions provide an efficient route to biallelic Apc inactivation. We also identified an additional 32 CIS genes/loci that may represent modifiers of the Apc(Min) phenotype. Five CIS genes tested for their role in proliferation caused a significant change in cell viability when message levels were reduced in human CRC cells. These findings demonstrate the utility of using transposon mutagenesis to identify low-frequency and cooperating cancer genes; this approach will aid in the development of combinatorial therapies targeting this deadly disease.

Indexed as

AnimalsCell Line, TumorColorectal NeoplasmsDNA Transposable ElementsGene SilencingGenetic Predisposition to DiseaseGenetic TestingHumansMiceMice, TransgenicMutagenesis, InsertionalRNA InterferenceRNA, Small InterferingDNA Transposable ElementsRNA, Small Interfering

Identifiers

PMID21436051
PMCPMC3078351
OpenAlexW2008118613

What OpenQuestion holds

Textmetadata
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.