Abstract:
:Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Clarke M,Mackay A,Ismer B,Pickles JC,Tatevossian RG,Newman S,Bale TA,Stoler I,Izquierdo E,Temelso S,Carvalho DM,Molinari V,Burford A,Howell L,Virasami A,Fairchild AR,Avery A,Chalker J,Kristiansen M,Haupfear K,Daltdoi
10.1158/2159-8290.CD-19-1030subject
Has Abstractpub_date
2020-07-01 00:00:00pages
942-963issue
7eissn
2159-8274issn
2159-8290pii
2159-8290.CD-19-1030journal_volume
10pub_type
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