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 PMID:29869612  

PAX3-FOXO1 transgenic zebrafish models identify HES3 as a mediator of rhabdomyosarcoma tumorigenesis.

Genevieve C Kendall | Sarah Watson | Lin Xu | Collette A LaVigne | Whitney Murchison | Dinesh Rakheja | Stephen X Skapek | Franck Tirode | Olivier Delattre | James F Amatruda
eLife | 2018

Alveolar rhabdomyosarcoma is a pediatric soft-tissue sarcoma caused by PAX3/7-FOXO1 fusion oncogenes and is characterized by impaired skeletal muscle development. We developed human PAX3-FOXO1 -driven zebrafish models of tumorigenesis and found that PAX3-FOXO1 exhibits discrete cell lineage susceptibility and transformation. Tumors developed by 1.6-19 months and were primitive neuroectodermal tumors or rhabdomyosarcoma. We applied this PAX3-FOXO1 transgenic zebrafish model to study how PAX3-FOXO1 leverages early developmental pathways for oncogenesis and found that her3 is a unique target. Ectopic expression of the her3 human ortholog, HES3, inhibits myogenesis in zebrafish and mammalian cells, recapitulating the arrested muscle development characteristic of rhabdomyosarcoma. In patients, HES3 is overexpressed in fusion-positive versus fusion-negative tumors. Finally, HES3 overexpression is associated with reduced survival in patients in the context of the fusion. Our novel zebrafish rhabdomyosarcoma model identifies a new PAX3-FOXO1 target, her3/HES3, that contributes to impaired myogenic differentiation and has prognostic significance in human disease.

Pubmed ID: 29869612

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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Zebrafish International Resource Center (tool)

RRID:SCR_005065

Center that supplies access to wild-type, mutant, and transgenic zebrafish lines, EST's/cDNAs, antibodies and fish health services. ZIRC Health Services include diagnostic pathology testing for zebrafish and other small laboratory fish species.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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FISHER (tool)

RRID:SCR_009181

THIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)

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Gene Ontology (tool)

RRID:SCR_002811

Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.

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Cuffdiff (tool)

RRID:SCR_001647

Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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OriGene (tool)

RRID:SCR_008985

A research tool company focused on the creation of the largest commercial collection of full-length human cDNAs in a standard expression vector. The availability of the complete human genome sequence and the subsequent development of genome-based tools have enabled the identification of relevant drug targets through system biology approaches. OriGene''s vision is to prepare comprehensive, genome wide research tools and technology platforms to enable scientists to study complete biological pathways, thus enabling a better understanding of disease mechanisms including cancer and stem cell research. OriGene Technologies uses high-throughput, genome wide approach to develop products for pharmaceutical, biotechnology, and academic research. Their flagship product is the cDNA clone collection, a searchable gene bank of over 30,000 human full-length TrueClone cDNA collection and over 25,000 TrueORF cDNA clones. From their TrueORF cDNA clones, they have developed the largest offering of full length human proteins expressed in mammalian cells, ideal for functional studies. Their TrueMAB project develops mouse monoclonal antibodies against protein antigens with the goal to develop protein assays for every human protein. They also offer complete molecular biology services from codon optimization, gene synthesis, protein expression and assay development. In addition, they offer unique gene expression products such as TissueScan cancer tissue qPCR arrays and tissue biorepository for biomarker discovery and validation.

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Cufflinks (tool)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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Microsoft Excel (tool)

RRID:SCR_016137

Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.

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Rh30 (tool)

RRID:CVCL_0041

Cell line Rh30 is a Cancer cell line with a species of origin Homo sapiens (Human)

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C2C12 (tool)

RRID:CVCL_0188

Cell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)

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TL (organism)

RRID:ZIRC_ZL86

Danio rerio with name from ZIRC.

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tp53zdf1/+ (AB) (organism)

RRID:ZIRC_ZL1057

Danio rerio with name from ZIRC.

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AB (organism)

RRID:ZIRC_ZL1

Danio rerio with name from ZIRC.

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WIK (organism)

RRID:ZIRC_ZL84

Danio rerio with name from ZIRC.

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