Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas
Open Access
- 24 September 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 10 (1), 1-13
- https://doi.org/10.1038/s41467-019-12187-5
Abstract
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.Funding Information
- Canadian Cancer Society Research Institute (702296)
- Gouvernement du Canada | Canadian Institutes of Health Research (159805)
- A Kids’ Brain Tumor Cure Foundation, aka The PLGA foundation
- RESTRACOMP of the Hospital for Sick Children Ontario Graduate Scholarship
- RESTRACOMP of the Hospital for Sick Children Garron Family Cancer Center
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