This report describes a model of rhabdomyosarcoma 2, PAX3-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 PAX3 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 PAX3 protein plays a role in neural development and myogenesis, but has not been well characterized.
Transgenic UAS lines have been generated that allow targeted expression of a human PAX3-FOXO1 fusion protein (Hsap\FOXO1::Hsap\PAX3) or the wild-type human Hsap\PAX3 gene in flies. When either the fusion protein or the wild-type PAX3 are highly expressed in muscle cells, phenotypes similar to PAX7-FOXO1 are observed (see FBhh0000453), with abnormal muscle morphology and myogenic tissue in the CNS. However, the effects are milder than that seen with the PAX7-FOXO1 fusion protein, even at signficantly higher levels of expression.
[updated Dec. 2016 by FlyBase; FBrf0222196]
[RHABDOMYOSARCOMA 2; RMS2](https://omim.org/entry/268220)
[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)
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]
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).
PAX3 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 PAX3 protein plays a role in neural development and myogenesis. [from Gene Cards, PAX3; 2016.12.13]
Many to one: human genes FOXO1, FOXO3, FOXO4, and FOXO6 are orthologous to the fly gene foxo (4 human to 1 Drosophila).
