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.

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas / Guerreiro Stucklin, A.S., Ryall, S., Fukuoka, K., Zapotocky, M., Lassaletta, A., Li, C., Bridge, T., Kim, B., Arnoldo, A., Kowalski, P.E., Zhong, Y., Johnson, M., Li, C., Ramani, A.K., Siddaway, R., Nobre, L.F., de Antonellis, P., Dunham, C., Cheng, S., Boue, D.R., et al.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019). [10.1038/s41467-019-12187-5]

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

de Antonellis P.;
2019

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.
2019
Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas / Guerreiro Stucklin, A.S., Ryall, S., Fukuoka, K., Zapotocky, M., Lassaletta, A., Li, C., Bridge, T., Kim, B., Arnoldo, A., Kowalski, P.E., Zhong, Y., Johnson, M., Li, C., Ramani, A.K., Siddaway, R., Nobre, L.F., de Antonellis, P., Dunham, C., Cheng, S., Boue, D.R., et al.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019). [10.1038/s41467-019-12187-5]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/900828
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