Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas
Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas
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DOI：
10.1002/gcc.20343
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发表时间：
2006-09-01
影响因子：
3.7
通讯作者：
Joos, Stefan
中科院分区：
文献类型：
--
作者：
Adamowicz, Martyna;Radlwimmer, Bernhard;Joos, Stefan
在软组织肉瘤中经常观察到5号染色体短臂的拷贝数增加和高水平扩增。为了确定该区域可能参与肿瘤进展的基因，我们使用DNA微阵列分析了34例软组织肉瘤（10例多型和8例去分化脂肪肉瘤，6例恶性纤维组织细胞瘤和10例恶性周围神经鞘肿瘤（MPNST）），其中包括418个BAC克隆，占染色体臂5p的99%。在7个肿瘤中，发现了不同的高水平扩增，影响了4个不同的亚区。从这些区域中选择TERT TRIO、SKP2、FBX032、NKD2、SLC6A3、IRX2、POLS、FYB、PTGER4和FGF10基因，根据其潜在的转致功能进行详细的定量表达分析（RQ-PCR）。其中，编码胍核苷酸交换因子的TR10在所有病例中一致过表达，而IRX2和NKD2均通过WNT途径参与发育过程的调节，仅在MPNSTs中表现出特征性表达。详细的非参数多维尺度分析进一步表明，TRIO、IRX2和NKD2的表达与基因拷贝数密切相关。总之，我们发现TRIO、IRX2和NKD2经常受到高水平扩增的影响，并以基因剂量依赖的方式上调。因此，这些基因代表了软组织肉瘤中5p扩增的候选靶点，并可能在该疾病的进展过程中发挥关键作用。(c) 2006 Wiley-Liss, Inc。
Copy number gains and high-level amplifications of the short arm of chromosome 5 are frequently observed in soft tissue sarcomas. To identify genes from this region possibly involved in tumor progression, we analyzed 34 soft tissue sarcomas (10 pleomorphic and 8 dedifferentiated liposarcomas, 6 malignant fibrous histiocytomas, and 10 malignant peripheral nerve sheath tumors (MPNST)) using a DNA microarray including 418 BAC clones representing 99% of chromosome arm 5p. In seven tumors, distinct high-level amplifications were identified affecting four different subregions. From these regions, genes TERT TRIO, SKP2, FBX032, NKD2, SLC6A3, IRX2, POLS, FYB, PTGER4, and FGF10 were selected for detailed quantitative expression analysis (RQ-PCR) based on their potential turnorigenic function. Of these, TR10, coding for a guanidine nucleotide exchange factor, was consistently overexpressed in all cases, while IRX2 and NKD2, both involved in the regulation of developmental processes via the WNT pathway, showed a characteristic expression only in MPNSTs. Detailed nonparametric multidimensional scaling analysis further showed that the expression of TRIO, IRX2, and NKD2 strongly correlated with the gene copy number. In conclusion, we found TRIO, IRX2, and NKD2 frequently affected by high-level amplifications as well as up-regulated in a gene-dosage dependent manner. Thus, these genes represent candidate targets of 5p amplifications in soft tissue sarcomas and might play a crucial role during the progression of this disease. (c) 2006 Wiley-Liss, Inc.