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Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma


Small cell osteosarcoma is a rare bone tumor of high-grade malignancy that most often arises in the metaphysis of long bones in the second decade of life. Cytogenetic and molecular genetic findings in small cell osteosarcoma are poorly defined. Conventional cytogenetic analysis of a small cell osteosarcoma arising in the proximal tibia of a 9-year-old male revealed a diploid chromosomal complement with complex structural rearrangements involving chromosomes 6, 16, and 17. Immunohistochemical assessment of p53 protein expression revealed nuclear p53 immunoreactivity in approximately 15% of the neoplastic cells. Subsequent fluorescence in situ hybridization (FISH) analyses confirmed loss of the p53 gene locus on the derivative chromosome 17 homolog and were negative for amplification of the MDM2, CDK4, c-MYC, HER-2/neu, CCND1, and COPS3 gene loci. To the best of our knowledge, this represents the first demonstration of monoallelic deletion of p53 in small cell osteosarcoma, suggesting that p53 alterations may play an important role in the development of small cell osteosarcoma as well as conventional osteosarcoma.

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This work was supported in part by the Nebraska State Department of Health (LB595) and NIH (P30 CA36727). Jun Nishio was supported by the Gladys Pearson Fellowship in Pediatric Cancer and Genetics. This study was performed in compliance with Institutional Review Board (IRB) regulations.

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Correspondence to Julia A. Bridge.

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Nishio, J., Gentry, J.D., Neff, J.R. et al. Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma. Virchows Arch 448, 852–856 (2006). https://doi.org/10.1007/s00428-006-0181-x

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  • Small cell osteosarcoma
  • p53
  • Cytogenetics
  • FISH