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首页> 外文期刊>Cellular oncology >Multiple splice variants of EWSR1-ETS fusion transcripts co-existing in the Ewing sarcoma family of tumors
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Multiple splice variants of EWSR1-ETS fusion transcripts co-existing in the Ewing sarcoma family of tumors

机译：尤因肉瘤家族中并存的EWSR1-ETS融合转录本的多个剪接变体

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Purpose: The Ewing sarcoma family of tumors (EFT) is characterized by fusions of the EWSR1 gene on chromosome 22q12 with either one of the genes encoding members of the ETS family of transcription factors, in the majority of cases FLI1 or ERG. Many alternative EWSR1-ETS gene fusions have been encountered, due to variations in the locations of the EWSR1 and ETS genomic breakpoints. The resulting heterogeneity in EWSR1-ETS fusion transcripts may further be increased by the occurrence of multiple splice variants within the same tumor. Here we present a retrospective study designed to detect all of the EWSR1-FLI1 and EWSR1-ERG fusion transcripts in a series of 23 fresh frozen EFT tissues. Methods: RT-PCR and nested fluorescent multiplex PCR were used to amplify EWSR1-FLI1 and EWSR1-ERG transcripts from EFT tissues. Fusion transcripts were identified by laser-induced fluorescent capillary electrophoresis and confirmed by sequence analysis. Results: Nine different EWSR1-FLI1 fusion transcripts and one EWSR1-ERG fusion transcript were identified in 21 out of 23 fresh frozen EFT tissue samples. In five cases multiple fusion transcripts were found to coexist in the same tumor sample. We additionally reviewed previous reports on twelve cases with multiple EWSR1-ETS fusion transcripts. Conclusions: Alternative splicing may frequently affect the process of EFT-associated fusion gene transcription and, as such, may significantly contribute to the pathogenic role of EFT-associated chromosome translocations. In a considerable number of cases this may result in multiple splice variants within the same tumor.
机译：目的：尤文氏肉瘤肿瘤家族（EFT）的特征在于，在大多数情况下，FLI1或ERG在22q12号染色体上的EWSR1基因与编码ETS转录因子家族成员的一种基因融合。由于EWSR1和ETS基因组断点位置的变化，已经遇到了许多替代性EWSR1-ETS基因融合体。 EWSR1-ETS融合转录本中产生的异质性可能会因同一肿瘤内多个剪接变体的出现而进一步增加。在这里，我们提出了一项回顾性研究，旨在检测一系列23种新鲜冷冻EFT组织中的所有EWSR1-FLI1和EWSR1-ERG融合转录本。方法：采用RT-PCR和巢式荧光多重PCR从EFT组织中扩增出EWSR1-FLI1和EWSR1-ERG转录本。通过激光诱导的荧光毛细管电泳鉴定融合转录本，并通过序列分析确认。结果：在23份新鲜的冷冻EFT组织样本中，有21份鉴定出9种不同的EWSR1-FLI1融合转录本和1份EWSR1-ERG融合转录本。在五种情况下，发现多个融合转录本共存于同一肿瘤样品中。我们还回顾了先前关于12例具有多个EWSR1-ETS融合转录本的病例的报告。结论：选择性剪接可能经常影响EFT相关融合基因的转录过程，因此，可能显着促进EFT相关染色体易位的致病作用。在相当多的情况下，这可能导致同一肿瘤内出现多个剪接变体。

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