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.

骨肉瘤是儿童、青少年和年轻人中最常见的恶性骨肿瘤。尽管骨肉瘤基因组中存在大量畸变，但迄今为止尚未发现复发的驱动突变。此外，与其他肉瘤实体不同，尚未报道由染色体重排产生的功能性融合蛋白。然而，骨肉瘤的部分遗传复杂性可能可以通过骨肉瘤与主要肿瘤抑制因子TP53的种系和体细胞突变的关联来解释，TP53保护基因组的完整性。通过证明导致转录活性融合基因的TP53启动子易位是骨肉瘤中反复发生的事件，Saba、Difilippo 等人最近发表的一篇文章对长期学习的范式提出了挑战。骨肉瘤似乎不再是一种融合阴性肿瘤，并且通过将TP53启动子反式激活为致癌融合伴侣的硬连线细胞应激反应，TP53可以被颠覆并转变为癌基因。