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General Information
Name
rhabdomyosarcoma 2, PAX7-FOXO1 fusion
FlyBase ID
FBhh0000453
Disease Ontology Term
Parent Disease
Overview

This report describes a model of rhabdomyosarcoma 2, PAX7-FOXO1 fusion. Rhabdomyosarcoma 2 is associated with translocations resulting in the fusion of the FOXO1 gene on chromosome 13 with either the PAX3 gene on chromosome 2 as a result of a translocation t(2;13), or with the PAX7 gene on chromosome 1 as a result of a translocation t(1;13). Both PAX7 and FOXO1 encode transcription factors. The FOXO1 protein binds to the insulin response element (IRE); it is a primary target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. The PAX7 protein is thought to play role in myogenesis, but has not been well characterized.

Transgenic UAS lines that allow targeted expression of a human PAX7-FOXO1 fusion protein (Hsap\FOXO1::Hsap\PAX7) in flies have been generated. When the fusion protein is expressed in muscle cells, the larval musculature exhibits gross abnormalities. In addition, mono-nucleated cells form and separate from syncytial myofibers, and then spread to nonmuscular tissue compartments, including the central nervous system. A similar, but much milder, phenotype is observed for a PAX3-FOXO1 fusion model (see FBhh0000454). These results support the hypothesis that rhabdomyosarcoma can originate from differentiated syncytial muscle cells. Expression of UAS-Hsap\FOXO1::Hsap\PAX7 using GAL4 drivers that result lethality has allowed identification of genetically interacting genes in flies (see below and in the report for Hsap\FOXO1::Hsap\PAX7).

[updated Dec. 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: rhabdomyosarcoma 2, PAX7-FOXO1 fusion
OMIM report

[RHABDOMYOSARCOMA 2; RMS2](https://omim.org/entry/268220)

Human gene(s) implicated

[PAIRED BOX GENE 7; PAX7](https://omim.org/entry/167410)

[PAIRED BOX GENE 3; PAX3](https://omim.org/entry/606597)

[FORKHEAD BOX O1A; FOXO1A](https://omim.org/entry/136533)

Symptoms and phenotype

Rhabdomyosarcoma (RMS) is a cancer made up of cells that normally develop into skeletal muscle, but have failed to fully differentiate. Rhabdomyosarcoma 2 is also called alveolar rhabdomyosarcoma; "alveolar" refers to the appearance of the affected muscle tissue (not to the lungs).

Alveolar rhabdomyosarcoma (ARMS) typically affects all age groups equally and most often occurs in large muscles of the trunk, arms, and legs. ARMS tends to develop more quickly than embryonal rhabdomyosarcoma (ERMS) and usually requires more intense treatment. [http://www.cancer.org/cancer/rhabdomyosarcoma/detailedguide/rhabdomyosarcoma-what-is-rhabdomyosarcoma]

Genetics

Alveolar rhabdomyosarcoma results from fusion of the PAX3 gene on chromosome 2 with the FOXO1 gene on chromosome 13 as a result of a translocation t(2;13), or from fusion of the PAX7 gene on chromosome 1 with the FOXO1 gene as a result of a translocation t(1;13).

Cellular phenotype and pathology
Molecular information

PAX7 is a member of the paired box (PAX) family of transcription factors; FOXO1 belongs to the forkhead family of transcription factors. The FOXO1 protein binds to the insulin response element (IRE); it is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress; its activity is suppressed by insulin. [from Gene Cards, FOXO1; 2016.12.13] The PAX7 protein is thought to play role in myogenesis through regulation of muscle precursor cells proliferation. [from Gene Cards, PAX7; 2016.12.13]

External links
Disease synonyms
RMS2
rhabdomyosarcoma, alveolar
RMSA
alveolar rhabdomyosarcoma
ARMS
rhabdomyosarcoma 2, alveolar
Search term: sarcoma
Search term: muscle cancer
Search term: cancer of skeletal muscle
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: the human genes PAX7 and PAX3 are high-scoring orthologs of fly genes prd, gsb, and gsb-n (2 human to 3 Drosophila).

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: human genes FOXO1, FOXO3, FOXO4, and FOXO6 are orthologous to the fly gene foxo (4 human to 1 Drosophila).

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (0)
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (0 groups)
    Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
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    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
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    Publicly Available Stocks
    References (10)