FB2025_05 , released December 11, 2025
Human Disease Model Report: rhabdomyosarcoma 2, PAX7-FOXO1 fusion
Open Close
General Information
Name
rhabdomyosarcoma 2, PAX7-FOXO1 fusion
FlyBase ID
FBhh0000453
Disease Ontology Term
Parent Disease
OMIM
RHABDOMYOSARCOMA 2; RMS2
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

[FORKHEAD BOX O1; FOXO1](https://omim.org/entry/136533)

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

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

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).

(FlyBase Curators, 2013-)

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]

(FlyBase Curators, 2013-)
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).

(OMIM, 2013-)
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]

(FlyBase Curators, 2013-)
External links
Disease synonyms
alveolar rhabdomyosarcoma
ARMS
rhabdomyosarcoma 2, alveolar
rhabdomyosarcoma, alveolar
RMS2
RMSA
Search term: cancer of skeletal muscle
Search term: muscle cancer
Search term: sarcoma
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
PAX7; paired box 7
D. melanogaster ortholog (based on DIOPT)
Dmel\prd
(DIOPT, 2013-)
Dmel\gsb
(DIOPT, 2013-)
Dmel\gsb-n
(DIOPT, 2013-)
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)
Symbol / Name
FOXO1; forkhead box O1
D. melanogaster ortholog (based on DIOPT)
Dmel\foxo
(DIOPT, 2013-)
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)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
      Hsap\FOXO1::Hsap\PAX7
      Models Based on Experimental Evidence ( 1 )
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Hsap\FOXO1::Hsap\PAX7UAS.cGa
      model of  alveolar rhabdomyosarcoma
      is ameliorated by Ras85De2F
      (Galindo et al., 2006)
      is exacerbated by Ras85DV12.UAS
      (Galindo et al., 2006)
      is ameliorated by Ras85De1B
      (Galindo et al., 2006)
      is ameliorated by Ras85D06677
      (Galindo et al., 2006)
      is ameliorated by rols08232
      (Avirneni-Vadlamudi et al., 2012)
      is ameliorated by Mef222-21
      (Galindo et al., 2014)
      is ameliorated by mamBG02477
      (Galindo et al., 2014)
      is ameliorated by mam2
      (Galindo et al., 2014)
      Alleles Representing Disease-Implicated Variants
      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
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Hsap\FOXO1::Hsap\PAX7UAS.cGa
      P{UAS-PAX7-FKHR.G}
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      References (10)