BACKGROUND Next generation sequencing (NGS) has increased the detection of fusion genes in cancer. NGS has found multiple fusions in single tumor samples; however, the incidence of this in pediatric soft tissue and bone tumors (PSTBTs) is not well documented. The aim of this study is to catalogue the incidence of multiple fusions in a series of PSTBTs, and apply a modified gene fusion classification system to determine clinical relevance. METHODOLOGY RNA from 78 bone and soft tissue tumors and 7 external quality assessment samples were sequenced and analyzed using recently-described Metafusion (MF) software and classified using a modification of previously-published schema for fusion classification into 3 tiers: 1, strong clinical significance; 2, potential clinical significance; and 3, unknown clinical significance. RESULTS One-hundred forty-five fusions were detected in 85 samples. Fifty-five samples (65%) had a single fusion and 30 (35%) had more than 1 fusion. No samples contained more than 1 tier 1 fusion. There were 40 tier 1 (28%), 36 tier 2 (24%), and 69 (48%) tier 3 fusions. CONCLUSIONS A significant percentage of PSTBTs harbor more than 1 fusion, and by applying a modified fusion classification scheme, the potential clinical relevance of such fusions can be determined.

中文翻译：

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一系列小儿软组织和骨肿瘤中多重融合的发生率。

背景技术下一代测序（NGS）增加了癌症中融合基因的检测。NGS 在单个肿瘤样本中发现了多个融合；然而，这种情况在儿科软组织和骨肿瘤（PSTBT）中的发生率尚无充分记录。本研究的目的是对一系列 PSTBT 中多重融合的发生率进行分类，并应用修改后的基因融合分类系统来确定临床相关性。方法学 使用最近描述的 Metafusion (MF) 软件对来自 78 个骨和软组织肿瘤和 7 个外部质量评估样本的 RNA 进行测序和分析，并使用先前发布的融合分类方案的修改将其分类为 3 层：1、强临床意义; 2、潜在的临床意义；3、临床意义不明。结果 在 85 个样本中检测到 145 个融合。55 个样本 (65%) 具有单一融合，30 个样本 (35%) 具有超过 1 个融合。没有样本包含超过 1 个 1 级融合。其中有 40 个 1 级融合（28%）、36 个 2 级融合（24%）和 69 个 3 级融合（48%）。结论 相当大比例的 PSTBT 具有超过 1 个融合，通过应用修改后的融合分类方案，可以确定此类融合的潜在临床相关性。