Chimeric RNAs and their encoded proteins have been traditionally viewed as unique features of neoplasia, and have been used as biomarkers and therapeutic targets for multiple cancers. Recent studies have demonstrated that chimeric RNAs also exist in non-cancerous cells and tissues, although large-scale, genome-wide studies of chimeric RNAs in non-diseased tissues have been scarce. Here, we explored the landscape of chimeric RNAs in 9495 non-diseased human tissue samples of 53 different tissues from the GTEx project. Further, we established means for classifying chimeric RNAs, and observed enrichment for particular classifications as more stringent filters are applied. We experimentally validated a subset of chimeric RNAs from each classification and demonstrated functional relevance of two chimeric RNAs in non-cancerous cells. Importantly, our list of chimeric RNAs in non-diseased tissues overlaps with some entries in several cancer fusion databases, raising concerns for some annotations. The data from this study provides a large repository of chimeric RNAs present in non-diseased tissues, which can be used as a control dataset to facilitate the identification of true cancer-specific chimeras.

中文翻译：

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非患病组织和细胞中嵌合 RNA 的景观。

嵌合 RNA 及其编码的蛋白质传统上被视为瘤形成的独特特征，并已被用作多种癌症的生物标志物和治疗靶点。最近的研究表明嵌合 RNA 也存在于非癌细胞和组织中，尽管对非患病组织中嵌合 RNA 的大规模、全基因组研究很少。在这里，我们探索了来自 GTEx 项目的 53 种不同组织的 9495 个非患病人体组织样本中嵌合 RNA 的景观。此外，我们建立了对嵌合 RNA 进行分类的方法，并在应用更严格的过滤器时观察到特定分类的富集。我们通过实验验证了来自每个分类的嵌合 RNA 子集，并证明了两种嵌合 RNA 在非癌细胞中的功能相关性。重要的，我们在非患病组织中的嵌合 RNA 列表与几个癌症融合数据库中的一些条目重叠，引起了对一些注释的担忧。这项研究的数据提供了存在于非患病组织中的大型嵌合 RNA 存储库，可用作控制数据集，以促进识别真正的癌症特异性嵌合体。