Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features

Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features
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DOI:
10.1016/j.biocel.2014.05.006
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发表时间:
2014-08-01
影响因子:
4
通讯作者:
Debiec-Rychter, Maria
Debiec-Rychter, Maria
中科院分区:
生物学2区
文献类型:
--
作者:
Przybyl, Joanna;Sciot, Raf;Debiec-Rychter, Maria

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简介:滑膜肉瘤(SynSa)是一种侵袭性间叶肿瘤,约占所有软组织肉瘤的10%。超过一半的SynSa患者发展转移或局部复发,但潜在的分子机制的侵略性的临床behaviors.Materials和方法:64个冷冻肿瘤标本54 SynSa患者进行阵列比较基因组杂交(aCGH)和基因表达谱。检查的肿瘤标本集包括16个来自未治疗患者的原发性肿瘤,这些患者未发生转移/局部复发(SynSa 1组),26例原发性肿瘤,来自随访期间发生转移或局部复发的未经治疗的患者(SynSa 2组)和22例异时转移性/复发性SynSa肿瘤结果:AURKA和KIF 18 A基因在SynSa 2和SynSa 3组中的表达较SynSa 1组显著上调,这两个基因在各种有丝分裂事件中起重要作用。SynSa 2和SynSa 3肿瘤的表达谱未显示任何显著差异。基于aCGH图谱的基因组指数(GI)分析表明,与SynSa 2和SynSa 3组相比,SynSa 1组的肿瘤基因组复杂性显著降低。SynSa 2和SynSa 3肿瘤之间的基因组复杂性没有显著差异。结论:原发性SynSa肿瘤发生转移或局部复发的患者与转移/复发肿瘤具有共同的分子特征。目前的数据表明,积极的临床SynSa行为是确定在肿瘤发生的早期,可能与有丝分裂机制的调节受损。(C)2014爱思唯尔有限公司版权所有。
Introduction: Synovial sarcoma (SynSa) is an aggressive mesenchymal tumor, comprising approximately 10% of all soft tissue sarcomas. Over half of SynSa patients develop metastasis or local recurrence, but the underlying molecular mechanisms of the aggressive clinical behavior remain poorly characterized.Materials and methods: Sixty-four frozen tumor specimens from 54 SynSa patients were subjected to array comparative genomic hybridization (aCGH) and gene expression profiling. The examined set of tumor specimens included 16 primary tumors from untreated patients who did not develop metastasis/local recurrence (SynSa1 group), 26 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (SynSa2 group), and 22 metachronous metastatic/recurrent SynSa tumors (SynSa3 group).Results: AURKA and KIF18A, which play important roles in various mitotic events, were the two most up-regulated genes in SynSa2 and SynSa3 groups compared to the SynSa1 group. Expression profiles of SynSa2 and SynSa3 tumors did not show any significant differences. Analysis of genomic index (GI) based on aCGH profiles demonstrated that the SynSa1 group consisted of tumors with significantly less complex genomes compared to SynSa2 and SynSa3 groups. There was no significant difference in genome complexity between SynSa2 and SynSa3 tumors.Conclusions: Primary SynSa tumors from patients who develop metastases or local recurrence share common molecular features with metastatic/recurrent tumors. Presented data suggest that the aggressive clinical SynSa behavior is determined early in tumorigenesis and might be related to impaired regulation of mitotic mechanisms. (C) 2014 Elsevier Ltd. All rights reserved.