Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike.

译文

:骨肉瘤是影响儿童和成人的原发性骨恶性肿瘤。在这里,我们介绍了迄今为止最大的骨肉瘤测序研究,包括112种儿童和成人肿瘤,涵盖了所有主要的组织学亚型。我们研究的关键发现是在8/112(7%)的病例中鉴定胰岛素样生长因子(IGF)信号基因的突变。我们在另外87个骨肉瘤中使用荧光原位杂交(FISH)验证了这一观察结果,并在14%的肿瘤中观察到了IGF1受体(IGF1R)扩增。这些发现可能会为将来在骨肉瘤中使用IGF1R抑制剂的患者选择药物提供依据。分析突变的模式,我们确定了独特的重排图谱,包括以色杆菌病和扩增为特征的过程。该过程在离散的基因组区域反复进行,并产生驱动突变。它可能代表了与年龄无关的突变机制,有助于儿童和成年人中骨肉瘤的发展。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录