Metabolomic analysis of Mdx mouse tumors

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Dystrophin the responsible gene for Duchenne muscular dystrophy is also regarded as a tumor suppressor because some DMD patients as well as mdx mouse spontaneously develop various tumors such as rhabdomyosarcoma and glioma.In FY2022, to understand the relationship of dystrophin defect and tumor development, the applicants have successfully established six mdx mice and observed them to spontaneously develop various tumors, respectively. The six tumors were characterized by immunohistochemical staining, and FISH analysis and divided into two groups: three rhabdomyosarcoma and three spindle cell sarcomas.The applicants next performed a comprehensive analysis of the hydrophilic metabolomic profile by Gas chromatography/Mass Spectrometry with cultured cells established from the tumors and compared the result to metabolites from skeletal muscle and among the two tumor types. 76 metabolites were identified with 20 metabolites that demonstrated a significantly higher fold change. Amongst the identified metabolites were many amino acids that function as alternative carbon source in glycolysis such as alanine, serine, aspartate and GABA, as well as sugars. Pathway analysis identified alanine, aspartate and glutamate metabolic pathway; taurine and hypotaurine pathway; TCA pathway; pyruvate metabolic pathway, pentose and glucuronic interconversion pathways etc.