Research Department of Pathology, University College London (UCL) Cancer Institute, London, UK.
Wellcome Sanger Institute, Hinxton, UK.
J Pathol Clin Res. 2021 Sep;7(5):425-431. doi: 10.1002/cjp2.219. Epub 2021 May 9.
Osteosarcoma, the most common primary malignant tumour of bone, affects both children and adults. No fundamental biological differences between paediatric and adult osteosarcoma are known. Here, we apply multi-region whole-genome sequencing to an index case of a 4-year-old child whose aggressive tumour harboured high-level, focal amplifications of MYC and CCNE1 connected by translocations. We reanalysed copy number readouts of 258 cases of high-grade osteosarcoma from three different cohorts and identified a significant enrichment of focal MYC, but not CCNE1, amplifications in children. Furthermore, we identified four additional cases of MYC and CCNE1 coamplification, highlighting a rare driver event which warrants further investigation. Our findings indicate that amplification of the MYC oncogene is a major driver of childhood osteosarcoma, while CCNE1 appears recurrently amplified independent of age.
骨肉瘤是最常见的原发性骨恶性肿瘤，可发生于儿童和成人。目前尚未发现儿童骨肉瘤和成人骨肉瘤之间存在根本的生物学差异。在这里，我们对一名 4 岁儿童的一个典型病例进行了多区域全基因组测序，该患儿侵袭性肿瘤中存在高水平、局灶性 MYC 和 CCNE1 的扩增，这些扩增通过易位连接。我们重新分析了来自三个不同队列的 258 例高级别骨肉瘤的拷贝数读数，并在儿童中发现了局灶性 MYC 扩增的显著富集，但 CCNE1 扩增不明显。此外，我们还鉴定了另外 4 例 MYC 和 CCNE1 共扩增的病例，突出了这一罕见的驱动事件，值得进一步研究。我们的研究结果表明，MYC 癌基因的扩增是儿童骨肉瘤的主要驱动因素，而 CCNE1 似乎与年龄无关，呈复发性扩增。
