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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
- 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
- Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency.
- Authors: Ho M, Post CM, Donahue LR, Lidov HG, Bronson RT, Goolsby H, Watkins SC, Cox GA, Brown RH Jr
- Issue date: 2004 Sep 15
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The Beeper [1999 Vol. 9, No. 11]Seigler, Peggy; Baker, Toni; Steele, Deborah; Simkins, Sally L.; Simkins, Sally L.; Division of Institutional Relations; Division of Strategic Support (Medical College of Georgia, 1999-06-03)Features this week include: MCG Children's Medical Center to fill airwaves; ID badge conversion nears completion; Tollison chair receives "distinguished" designation; MCG participates in international breast cancer reduction study; Relay for Life draws supporter from throughout campus; First dental CD due this Fall; Testing may affect computer systems; Toxin may take away tightness and pain; Dr. Ellison receives Hardman Cup; Support groups offer help for cancer patients; UAB professor to address symposium; Commissions, committees appointed to study MCG future; Ultrasound enhances pregnancy care; Calcium important part of diet; Counseling available for faculty and staff; P.A. students participate in health fair; Are you at risk for Stroke?; Diabetes isn't 'same old disease'; Special collections room hold history.
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