Evidence map›Paper›PMID 25961939›Full record

ArticleNature genetics2015

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis.

Branden S Moriarity, George M Otto, Eric P Rahrmann, Susan K Rathe, Natalie K Wolf, Madison T Weg, Luke A Manlove, Rebecca S LaRue, Nuri A Temiz, Sam D Molyneux and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed, 2 pooled it
23.7field-weighted citation impact, top 1% 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

158 citing papers in PubMed, 2 syntheses or guidelines pooled it, 244 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Journal for immunotherapy of cancer · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Mesenchymal stroma drives axonogenesis and nerve-induced aggressiveness in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2025
    Article
  11. Article
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  13. Review
  14. Article
  15. Article
  16. Review
  17. Cancers · 2024
    Article
  18. Article
  19. Article
  20. Article

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

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

23 authors at 8 institutions in 3 countries.

Branden S Moriarity1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
George M Otto1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [4] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Eric P Rahrmann1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [4] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Susan K RatheMasonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Natalie K Wolf1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Madison T Weg1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Luke A ManloveDepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Rebecca S LaRue1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Nuri A TemizMasonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000000314163639
Sam D MolyneuxOntario Cancer Institute, Toronto, Ontario, Canada.
Kwangmin ChoiDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Kevin J HollyDepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Aaron L SarverMasonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Milcah C Scott1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, Minnesota, USA.
Colleen L ForsterBioNet, Academic Health Center, University of Minnesota, Minneapolis, Minnesota, USA.
Jaime F Modiano1] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [2] Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, Minnesota, USA. [3] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Chand KhannaTumor and Metastasis Biology Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
Stephen M HewittTissue Array Research Program (TARP), Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
Rama KhokhaOntario Cancer Institute, Toronto, Ontario, Canada.
Yi YangDepartment of Orthopedic Surgery, Musculoskeletal Tumor Center, People's Hospital, Peking University, Beijing, China.
Richard Gorlick1] Department of Pediatrics, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA. [2] Department of Molecular Pharmacology, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA.
Michael A DyerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
David A Largaespada1] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. [2] Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA. [3] Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. [4] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
University of Minnesota · USUniversity of Minnesota Medical Center · USNational Cancer Institute · USOntario Institute for Cancer Research · CAAlbert Einstein College of Medicine · USCincinnati Children's Hospital Medical Center · USPeking University · CNSt. Jude Children's Research Hospital · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
Musculoskeletal Training GrantT32AR050938 · NIAMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI CLOHISY, DENIS R · 2004 to 2020
$3.0M
Sleeping Beauty for uncovering cancer genes in miceR01CA113636 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW · 2006 to 2016
$2.5M
NCATS NIH HHS UL1 TR002494NCI NIH HHS P30 CA013330NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA113636NIAMS NIH HHS AR050938NIAMS NIH HHS T32 AR050938
6 · The paper itself

Abstract

Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma.

Indexed as

AnimalsBone NeoplasmsCarcinogenesisCell Line, TumorDNA Transposable ElementsDogsGenetic Predisposition to DiseaseGenomic InstabilityHumansMice, TransgenicMutagenesis, InsertionalOsteosarcomaPTEN PhosphohydrolaseSemaphorinsTumor Suppressor Protein p53DNA Transposable ElementsPTEN PhosphohydrolasePten protein, mouseSema4d protein, mouseSema6d protein, mouseSemaphorinsTumor Suppressor Protein p53

Identifiers

PMID25961939
PMCPMC4767150
OpenAlexW1699214082

What OpenQuestion holds

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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.