Evidence map›Paper›PMID 25129143›Full record

ArticleNature genetics2014

Human somatic cell mutagenesis creates genetically tractable sarcomas.

Sam D Molyneux, Paul D Waterhouse, Dawne Shelton, Yang W Shao, Christopher M Watling, Qing-Lian Tang, Isaac S Harris, Brendan C Dickson, Pirashaanthy Tharmapalan, Geir K Sandve and 9 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. CRISPR: A new paradigm of theranostics.Nanomedicine : nanotechnology, biology, and medicine · 2021
    Review
  6. Review
  7. Ex Vivo Transposon-Mediated Genetic Screens for Cancer Gene Discovery.Methods in molecular biology (Clifton, N.J.) · 2019
    Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Cancer gene discovery goes mobile.Nature genetics · 2014
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 4 countries.

Sam D MolyneuxDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Paul D WaterhouseDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Dawne SheltonDigital-biology Center, Bio-Rad Laboratories, Pleasanton, California, USA.
Yang W ShaoDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Christopher M WatlingDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Qing-Lian TangDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Isaac S HarrisDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Brendan C DicksonDepartment of Pathology and Division of Orthopaedic Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
Pirashaanthy TharmapalanDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Geir K SandveDepartment of Informatics, University of Oslo, Blindern, Oslo, Norway.ORCID 0000000249591409
Xiaoyang ZhangDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Swneke D BaileyDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Hal BermanDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Jay S WunderDepartment of Pathology and Division of Orthopaedic Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
Zsuzsanna IzsvákMax-Delbruck-Center for Molecular Medicine, Berlin, Germany.
Zsuzsanna IszvakMax-Delbruck-Center for Molecular Medicine, Berlin, Germany.
Mathieu LupienDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Tak W MakDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Rama KhokhaDepartment of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Ontario Institute for Cancer Research · CAMount Sinai Hospital · CABio-Rad (United States) · USMax Delbrück Center · DEUniversity of Oslo · NO

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Creating spontaneous yet genetically tractable human tumors from normal cells presents a fundamental challenge. Here we combined retroviral and transposon insertional mutagenesis to enable cancer gene discovery starting with human primary cells. We used lentiviruses to seed gain- and loss-of-function gene disruption elements, which were further deployed by Sleeping Beauty transposons throughout the genome of human bone explant mesenchymal cells. De novo tumors generated rapidly in this context were high-grade myxofibrosarcomas. Tumor insertion sites were enriched in recurrent somatic copy-number aberration regions from multiple cancer types and could be used to pinpoint new driver genes that sustain somatic alterations in patients. We identified HDLBP, which encodes the RNA-binding protein vigilin, as a candidate tumor suppressor deleted at 2q37.3 in greater than one out of ten tumors across multiple tissues of origin. Hybrid viral-transposon systems may accelerate the functional annotation of cancer genomes by enabling insertional mutagenesis screens in higher eukaryotes that are not amenable to germline transgenesis.

Indexed as

Mutagenesis, InsertionalCell LineDNA Transposable ElementsGenetic VectorsGenome, HumanHEK293 CellsHumansRetroviridaeRNA-Binding ProteinsSarcomaDNA Transposable Elementshigh density lipoprotein binding proteinRNA-Binding Proteins

Identifiers

PMID25129143
OpenAlexW1965888676

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.