Regional perturbation of gene transcription associated with intrachromosomal rearrangements in high grade ovarian cancer. Homo sapiens

Genomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, the more subtle relationship between rearrangements and expression changes in cancers has not been studied. Here, we demonstrate that significant regional overexpression of intact genes can occur in proximity to novel gene fusions, revealing neighboring gene overexpression as a previously unrecognized mechanism through which cancer cells remodel their transcriptomes.

基因组重排（Genomic rearrangements）是癌症生物学与疾病进展的标志性特征，可通过调控结构改变、表达模式变化、信号通路重编程以及基因融合（gene fusion）事件产生新型转录本，推动细胞发生快速转化。尽管编码致癌蛋白（oncogenic proteins）的功能性基因融合是基因组重排最显著的结局，但癌症中重排与表达变化之间更为微妙的关联尚未得到研究。本研究证实，完整基因可在新型基因融合附近出现显著的区域过表达，这揭示了邻近基因过表达——一种此前未被认知的癌细胞重塑转录组（transcriptomes）的机制。