Alterations of thep53, Rb andMDM2 genes in osteosarcoms
- 132 Downloads
Molecular defects affecting tumor-suppressor genes are an important step in the genesis of sarcomas. For example, inheritance of a defectiveRb orp53 gene predisposes the carrier to develop osteosarcoma, among other malignancies. In this study, we have assessed the occurrence ofp53, Rb andMDM2 alterations in the same samples of osteosarcomas, along with representative samples of various other sarcomas. Point mutations of thep53 gene were found in 13 of 42 osteosarcomas and 1 of 8 leiomyosarcomas, and gross rearrangement of thep53 gene was demonstrated in 5 of 37 osteosarcomas. The retinoblastoma susceptibility gene (Rb) was either rearranged or deleted in 7 of 37 osteosarcomas, 1 of 7 soft-tissue sarcomas and 1 of 4 Ewing sarcomas. Remarkably, 5 of the osteosarcomas havingRb alterations also hadp53 mutations. Amplification and overexpression of theMDM2 oncogene may lead to increasedMDM2-p53 binding resulting in inactivation ofp53 function. A two- to threefold increase in the copy number ofMDM2 was detected in 7 of 37 samples, 5 of which were osteosarcomas. Amplification of theMDM2 gene occurred independently ofp53 mutation; one sample having threefold amplification ofMDM2 also had ap53 mutation. In summary, 34 alterations of thep53, Rb andMDM2 genes were found in 26 of 42 (62%) osteosarcomas.
Key wordsp53 Rb MDMZ Osteosarcoma Sarcoma
Unable to display preview. Download preview PDF.
- Carbone D, Chiba I, Mitsudomi T (1991) Polymorphism at codon 213 within thep53 gene. Oncogene 6:91–92Google Scholar
- McCormick F, Harlow E (1980) Association of a murine 53,000-dalton phosphoprotein with simian virus 40 large-T antigen in transformed cells. J Virol 3:213–224Google Scholar
- Pedeutour F, Suijkerbuijk RF, Forus A, Van Gaal J, Van de Klundert W, Coindre JM, Nicolo G, Collin F, Van Haelst U, Huffermann K, Turc-Carel C (1994) Complex composition and coamplification ofSAS andMDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma. Genes Chromosomes Cancer 10:85–94PubMedGoogle Scholar
- Reifenberger G, Reifenberger J, Ichimura K, Meltzer PS, Collins VP (1994) Amplification of multiple genes from chromosomal region 12q13-14 in human malignant gliomas: preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2. Cancer Res 54:4299–4303PubMedGoogle Scholar