Amplification and overexpression of genes in 17p11.2 ~ p12 in osteosarcoma.
We summarize and briefly discuss recent findings with respect to the amplification and overexpression of candidate oncogenes in 17p11.2 ~p12 in high-grade osteosarcomas. Amplification of this region occurs in about 25% of cases. The amplification profiles are often complex and suggest the involvement of more than one oncogene. The 17p11.2 ~ p12 region harbors many low-copy repeats (LCRs). We propose LCR-mediated repeated duplication by mitotic nonallelic homologous recombination as mechanism for the generation of the amplifications in this region. Genes PMP22 and COPS3 and three expressed sequence tags from within 17p11.2 ~ p12 have been found to be frequently overexpressed and consistently overexpressed after amplification, which identifies them as candidate oncogenes in this region. Overexpression of COPS3 has been linked to TP53 protein degradation and, being equivalent to TP53 mutation, the induction of genomic instability, which frequently occurs in high-grade osteosarcoma. These findings may serve as a framework for future work aimed to identify the causative oncogenes in 17p11.2 ~p12, to clarify the mechanism of their amplification, and to determine their importance in osteosarcoma tumorigenesis.
Department of Human Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Maaike
M
van Dartel
Theo J M
TJ
Hulsebos
D001859:Bone Neoplasms / Q000235:genetics*; D000075686:COP9 Signalosome Complex; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D020224:Expressed Sequence Tags; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D009185:Myelin Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012516:Osteosarcoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C477661:COPS3 protein, human; D004273:DNA, Neoplasm; D009185:Myelin Proteins; D009363:Neoplasm Proteins; C073687:PMP22 protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D000075686:COP9 Signalosome Complex