Kiuru-Kuhlefelt S, El-Rifai W, Fanburg-Smith J, Kere J, Miettinen M, Knuutila S
Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Cytogenet Cell Genet. 2001;92(3-4):192-5. doi: 10.1159/000056901.
Dermatofibrosarcoma protuberans (DFSP) is a tumor of low or intermediate malignant potential with a tendency for recurrence, but low rate of metastasis. The tumorigenesis of DFSP has recently been shown to be associated with the fusion of the collagen type I alpha 1 (COL1A1) and platelet-derived growth factor B-chain (PDGFB) genes, often as a consequence of translocation t(17;22)(q22;q13). Cytogenetically, DFSP is often characterized by supernumerary ring chromosomes containing material from chromosomes 17 and 22. A subset of DFSPs undergo fibrosarcomatous transformation de novo or upon recurrence, and contain components indistinguishable from fibrosarcoma (FS-DFSP). The fibrosarcomatous transformation appears to carry an increased risk for recurrence and metastasis, and is considered to represent tumor progression. The molecular cytogenetic events contributing to tumor progression are unknown. We used comparative genomic hybridization to analyze DNA copy number changes in 11 cases of typical DFSP and 10 cases of FS-DFSP. All cases in both groups were found to exhibit a gain or high-level amplification on chromosome 17q and the majority also on 22q. This finding is in line with previous studies, and suggests further that not only the COL1A1/PDGFB fusion gene formation but also the role of DNA copy number gains in the 17q and 22q regions is crucial per se in the pathogenesis of DFSP. Even though FS-DFSPs displayed a trend toward increase in the number of DNA copy number changes, the difference was not statistically significant, which indicates that mechanisms other than copy number changes are important in the transformation process of DFSP.
隆突性皮肤纤维肉瘤（DFSP）是一种具有低或中度恶性潜能的肿瘤，有复发倾向，但转移率较低。最近研究表明，DFSP的肿瘤发生与I型胶原α1（COL1A1）基因和血小板衍生生长因子B链（PDGFB）基因的融合有关，这通常是17号染色体长臂2区2带（17q22）和22号染色体长臂1区3带（22q13）易位的结果。细胞遗传学上，DFSP通常特征为含有17号和22号染色体物质的额外环状染色体。一部分DFSP会新发或复发时发生纤维肉瘤转化，并含有与纤维肉瘤（FS-DFSP）无法区分的成分。纤维肉瘤转化似乎会增加复发和转移风险，被认为代表肿瘤进展。导致肿瘤进展的分子细胞遗传学事件尚不清楚。我们使用比较基因组杂交技术分析了11例典型DFSP和10例FS-DFSP的DNA拷贝数变化。两组所有病例均发现17号染色体长臂（17q）有增益或高水平扩增，大多数病例在22号染色体长臂（22q）也有此情况。这一发现与之前的研究一致，进一步表明不仅COL1A1/PDGFB融合基因的形成，而且17q和22q区域DNA拷贝数增加本身在DFSP的发病机制中也至关重要。尽管FS-DFSP显示出DNA拷贝数变化数量有增加的趋势，但差异无统计学意义，这表明除拷贝数变化外的其他机制在DFSP的转化过程中也很重要。
