Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney
Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney
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DOI：
10.18632/oncotarget.5882
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Pession, Andrea
中科院分区：
文献类型：
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作者：
Astolfi, Annalisa;Melchionda, Fraia;Pession, Andrea
目的：肾透明细胞肉瘤（CCSK）是一种罕见的儿童肾脏肿瘤，由于其组织学异质性，通常难以与其他儿童肾脏肿瘤区分。这项工作评估了一系列CCSK样本进行全转录组测序（WTS）的遗传异常，以确定分子生物标志物，可以提高诊断processed.Methods：WTS进行肿瘤RNA从8例CCSK。执行生物信息学分析，并实施用于检测基因内重排的管道。结果：WTS检测未发现任何SNVs、Ins/Del或融合事件。相反，基因内重排的分析使得能够在所有样品中检测BCOR转录物内的断点。在BCOR基因第15外显子检测到3个不同的框内ITD。ITD的存在被证实在肿瘤DNA和cDNA上，并导致BCOR的过表达。结论：WTS结合特异性生物信息学分析能够检测罕见的遗传事件，如基因内重排。BCOR最后一个外显子的ITD在所有分析的CCSK样本中都是复发性的，这代表了一个有价值的分子标志物，以提高这种罕见的儿童肾脏肿瘤的诊断。
Purpose: Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor that is frequently difficult to distinguish among other childhood renal tumors due to its histological heterogeneity. This work evaluates genetic abnormalities carried by a series of CCSK samples by whole transcriptome sequencing (WTS), to identify molecular biomarkers that could improve the diagnostic process.Methods: WTS was performed on tumor RNA from 8 patients with CCSK. Bioinformatic analysis, with implementation of a pipeline for detection of intragenic rearrangements, was executed. Sanger sequencing and gene expression were evaluated to validate BCOR internal tandem duplication (ITD).Results: WTS did not identify any shared SNVs, Ins/Del or fusion event. Conversely, analysis of intragenic rearrangements enabled the detection of a breakpoint within BCOR transcript recurrent in all samples. Three different in-frame ITD in exon15 of BCOR, were detected. The presence of the ITD was confirmed on tumor DNA and cDNA, and resulted in overexpression of BCOR.Conclusion: WTS coupled with specific bioinformatic analysis is able to detect rare genetic events, as intragenic rearrangements. ITD in the last exon of BCOR is recurrent in all CCSK samples analyzed, representing a valuable molecular marker to improve diagnosis of this rare childhood renal tumor.