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AbstractRhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and domestic mammals. The A/J inbred strain developed a high frequency (between 70â 80%) of adult pleomorphic type (APT) RSC at >20 months of age while BALB/cByJ also develop RSC but less frequently. These neoplasms invaded skeletal muscle surrounding either the axial or proximal appendicular skeleton and were characterized by pleomorphic cells with abundant eosinophilic cytoplasm, multiple nuclei, and cross striations. The diagnosis was confirmed by detection of alpha-sarcomeric actin and myogenin in the neoplastic cells using immunocytochemistry. The A/J strain, but not the related BALB/c substrains, is also characterised by a progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type 2B. The association between the development of RSC in similar muscle groups to those most severely affected by the progressive muscular dystrophy suggested that these neoplasms developed from abnormal regeneration of the skeletal muscle exacerbated by the dysferlin mutation. Transcriptome analyses of RSCs revealed marked downregulation of genes in muscular development and function signaling networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and Kcnj12 suggesting these may be important in the pathogenesis of RSC. These studies suggest that A strains of mice can be useful models for dissecting the molecular genetic basis for development, progression, and ultimately for testing novel anticancer therapeutic agents dealing with rhabdomyosarcoma.
CitationPLoS One. 2011 Aug 10; 6(8):e23498
- Skeletal muscle rhabdomyosarcomas in inbred laboratory mice.
- Authors: Sundberg JP, Adkison DL, Bedigian HG
- Issue date: 1991 May
- Dystrophin and dysferlin double mutant mice: a novel model for rhabdomyosarcoma.
- Authors: Hosur V, Kavirayani A, Riefler J, Carney LM, Lyons B, Gott B, Cox GA, Shultz LD
- Issue date: 2012 May
- Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development.
- Authors: Tostar U, Malm CJ, Meis-Kindblom JM, Kindblom LG, Toftgård R, Undén AB
- Issue date: 2006 Jan
- Mice lacking dystrophin or alpha sarcoglycan spontaneously develop embryonal rhabdomyosarcoma with cancer-associated p53 mutations and alternatively spliced or mutant Mdm2 transcripts.
- Authors: Fernandez K, Serinagaoglu Y, Hammond S, Martin LT, Martin PT
- Issue date: 2010 Jan
- Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers.
- Authors: Furlong MA, Mentzel T, Fanburg-Smith JC
- Issue date: 2001 Jun
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