Identification of the 12q15 amplicon within the homogeneously staining regions in the embryonal rhabdomyosarcoma cell line RMS-YM.
Gene amplification represents one of the molecular mechanisms of oncogene overexpression in many types of tumors. Homogeneously staining regions (HSRs) are cytogenetic hallmarks of gene amplification. Rhabdomyosarcoma is the most common malignant soft-tissue tumor in children. RMS-YM is an embryonal rhabdomyosarcoma cell line that possesses 3 HSRs. This cytogenetic finding suggests the presence of gene amplifications associated with tumor development or progression in RMS-YM. Here, using fluorescence in situ hybridization, we detected high amplification of the MDM2 gene in the HSRs of RMS-YM. We also refined the region of the amplicon and identified that the FRS2 gene and others are amplified in RMS-YM. MDM2 and FRS2 play important roles as a regulator of p53 and a mediator of FGF signaling, respectively, and thus are potential molecular targets for therapy in many different tumors. RMS-YM may be useful for studies of the molecular pathways of tumorigenesis and tumor progression in rhabdomyosarcoma and for in vitro evaluation of newly developed therapeutic agents that target MDM2 or FRS2.
Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Izumo, Japan.
N
N
Kakazu
H
H
Yamane
M
M
Miyachi
K
K
Shiwaku
H
H
Hosoi
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D045744:Cell Line, Tumor; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009857:Oncogenes; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C106534:FRS2 protein, human; D008565:Membrane Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2