文章：

TP53启动子易位重编程应激反应至骨肉瘤致癌效应因子

TP53 promoter translocations rewire stress responses to oncogenic effectors in osteosarcoma 

原文发布日期：2024-02-26 

英文摘要：

Osteosarcoma is the most prevalent malignant bone tumour in children, adolescents and young adults. Despite a multitude of aberrations present in osteosarcoma genomes, no recurrent driver mutations have been identified to date. In addition, unlike for other sarcoma entities, no functional fusion proteins resulting from chromosomal rearrangements have been reported. Part of the genetic complexity of osteosarcoma might, however, be explained by the association of osteosarcoma with germline and somatic mutations of the major tumour suppressor TP53 that safeguards genomic integrity. By demonstrating that TP53 promoter translocations resulting in transcriptionally active fusion genes are a recurrent event in osteosarcoma, long-learnt paradigms are challenged by a recent publication by Saba, Difilippo et al. Osteosarcoma no longer appears to be a fusion-negative tumour, and by hardwiring cellular stress responses that transactivate the TP53 promoter to an oncogenic fusion partner, TP53 can be subverted and turned into an oncogene. 

摘要翻译：

骨肉瘤是儿童、青少年及年轻成人中最常见的恶性骨肿瘤。尽管骨肉瘤基因组中存在大量变异，但迄今为止尚未发现复发性驱动突变。此外，与其他肉瘤类型不同，目前尚未报道由染色体重排导致的功能性融合蛋白。然而，骨肉瘤的部分遗传复杂性可能与其和主要肿瘤抑制基因TP53的种系及体细胞突变相关——该基因本是基因组完整性的守护者。Saba、Difilippo等人的最新研究打破了长期以来的认知范式：他们证实导致转录活性融合基因的TP53启动子易位是骨肉瘤中的复发性事件。骨肉瘤不再是无融合基因的肿瘤，通过将反式激活TP53启动子的细胞应激反应与致癌融合伙伴硬连线，TP53可被颠覆并转化为癌基因。

原文链接：

TP53 promoter translocations rewire stress responses to oncogenic effectors in osteosarcoma