Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas
Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas
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DOI：
10.1038/s41467-019-12187-5
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发表时间：
2019-09-25
影响因子：
16.6
通讯作者：
Hawkins, Cynthia
中科院分区：
文献类型：
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作者：
Stucklin, Ana S. Guerreiro;Boue, Daniel R.;Hawkins, Cynthia
与儿童和成人的神经胶质瘤相比，婴儿神经胶质瘤具有矛盾的临床行为：低级别肿瘤具有较高的死亡率，而高级别肿瘤具有更好的结果。然而，我们对其生物学知之甚少，因此无法解释这种行为，也无法解释最佳临床管理的构成。在这里，我们报告了对国际临床注释婴儿神经胶质瘤队列的全面遗传分析，揭示了 3 个临床亚组。第 1 组肿瘤出现在大脑半球，并存在受体酪氨酸激酶 ALK、ROS1、NTRK 和 MET 的改变。这些通常是单一事件并产生中间结果。第 2 组和第 3 组神经胶质瘤含有 RAS/MAPK 通路突变，分别出现在半球和中线。第 2 组肿瘤具有出色的长期生存率，而第 3 组肿瘤进展迅速且对放化疗反应不佳。我们得出结论，婴儿神经胶质瘤包含 3 个亚组，证明需要专门的治疗策略。
Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.