Gene Expression Profiling of Synovial Sarcoma: Distinct Signature of Poorly Differentiated Type

Gene Expression Profiling of Synovial Sarcoma: Distinct Signature of Poorly Differentiated Type
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DOI:
10.1097/pas.0b013e3181f7ce2c
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发表时间:
2010-11-01
影响因子:
5.6
通讯作者:
Ichikawa, Hitoshi
Ichikawa, Hitoshi
中科院分区:
医学1区
文献类型:
--
作者:
Nakayama, Robert;Mitani, Sachiyo;Ichikawa, Hitoshi

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低分化型滑膜肉瘤(PDSS)是滑膜肉瘤的一种变异型,其特征是细胞形态以圆形或短梭为主。虽然从临床病理研究中积累的证据表明这种滑膜肉瘤的变异与预后不良有很强的相关性,但关于PDSS的分子基础的报道很少。为了深入了解PDSS的发生机制(S),我们利用寡核苷酸芯片分析了34例滑膜肉瘤临床标本的基因表达谱,其中包括5例PDSS。在一项非监督分析中,34个样本分为3组,与组织学亚型密切相关:单相型、双相型和低分化型。PDSS的特征是与神经元和骨骼发育以及细胞黏附相关的基因下调。此外,还发现了一个特定染色体上的基因上调,即8q21.11。通过对另外9个滑膜肉瘤样本的逆转录-聚合酶链式反应分析,证实了该基因在PDSS中的特异性转录激活。我们的结果表明,根据表达谱,PDSS肿瘤构成了一个不同的组。
Poorly differentiated type synovial sarcoma (PDSS) is a variant of synovial sarcoma characterized by predominantly round or short-spindled cell morphology. Although accumulating evidence from clinicopathologic studies suggests a strong association between this variant of synovial sarcoma and poor prognosis, little has been reported on the molecular basis of PDSS. To gain insights into the mechanism(s) that underlie the emergence of PDSS, we analyzed the gene expression profiles of 34 synovial sarcoma clinical samples, including 5 cases of PDSS, using an oligonucleotide microarray. In an unsupervised analysis, the 34 samples fell into 3 groups that correlate closely with histologic subtypes: monophasic, biphasic, and poorly differentiated types. PDSS was characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion. Moreover, upregulation of genes on a specific chromosomal locus, 8q21.11, was identified. This locus-specific transcriptional activation in PDSS was confirmed by reverse transcriptase-PCR analysis of 9 additional synovial sarcoma samples. Our results indicate that PDSS tumors constitute a distinct group based on expression profiles.