源自两个基因的嵌合转录本 (CT) 产生的分子和功能多样性有助于肿瘤细胞的存活。目前还存在一些差距。本研究是对癌症基因组图谱 (TCGA) (https://portal.gdc.cancer.gov) 中 160 个卵巢癌样本的 RNA 测序数据集中确定的 CT 谱进行的系统研究。结构注释揭示了伴侣基因的染色体定位、差异剪接和调节非翻译区域的包含所带来的复杂性。表型特异性关联的识别进一步解决了转化过程中动态调节的间充质特征。在进化背景上，蛋白质编码 CT 被认为是高度保守的，而非编码 CT 可能是最近才进化的。我们还意识到，目前假定结构改变或邻近基因通读生成 CT 的前提在亲本基因在基因组上距离较远的情况下是无效的。在解决这一缺陷时，我们确定了 3D 空间中特定时空排列介导的基因邻近度对于生成 CT 的重要性。所有这些特征共同表明，通过平行或与本地调控网络串扰形成嵌合体来增加细胞中分子多样性的非随机机制。© 2023 作者。

The molecular and functional diversity generated by chimeric transcripts (CTs) that are derived from two genes is indicated to contribute to tumor cell survival. Several gaps yet exist. The present research is a systematic study of the spectrum of CTs identified in RNA sequencing datasets of 160 ovarian cancer samples in the The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov). Structural annotation revealed complexities emerging from chromosomal localization of partner genes, differential splicing and inclusion of regulatory, untranslated regions. Identification of phenotype-specific associations further resolved a dynamically modulated mesenchymal signature during transformation. On an evolutionary background, protein-coding CTs were indicated to be highly conserved, while non-coding CTs may have evolved more recently. We also realized that the current premise postulating structural alterations or neighbouring gene readthrough generating CTs is not valid in instances wherein the parental genes are genomically distanced. In addressing this lacuna, we identified the essentiality of specific spatiotemporal arrangements mediated gene proximities in 3D space for the generation of CTs. All these features together suggest non-random mechanisms towards increasing the molecular diversity in a cell through chimera formation either in parallel or with cross-talks with the indigenous regulatory network.© 2023 The Authors.