van Dartel Maaike, Hulsebos Theo J M
Department of Human Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Cancer Genet Cytogenet. 2004 Aug;153(1):77-80. doi: 10.1016/j.cancergencyto.2004.03.007.
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.
我们总结并简要讨论了近期关于高级别骨肉瘤中17p11.2p12区域候选癌基因扩增和过表达的研究结果。该区域的扩增发生在约25%的病例中。扩增图谱通常很复杂，提示不止一个癌基因参与其中。17p11.2p12区域含有许多低拷贝重复序列（LCR）。我们提出有丝分裂非等位基因同源重组介导的LCR重复复制是该区域产生扩增的机制。已发现基因PMP22和COPS3以及17p11.2p12区域内的三个表达序列标签经常过表达，且在扩增后持续过表达，这将它们确定为该区域的候选癌基因。COPS3的过表达与TP53蛋白降解有关，并且等同于TP53突变，可诱导基因组不稳定，这在高级别骨肉瘤中经常发生。这些发现可为未来的研究工作提供框架，旨在鉴定17p11.2p12区域的致病癌基因，阐明其扩增机制，并确定它们在骨肉瘤肿瘤发生中的重要性。
