Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Matthew Clarke, Alan Mackay, Britta Ismer, Jessica C. Pickles, Ruth G. Tatevossian, Scott Newman, Tejus A. Bale, Iris Stoler, Elisa Izquierdo, Sara Temelso, Diana M. Carvalho , Valeria Molinari , Anna Burford, Louise Howell, Alex Virasami , Amy R. Fairchild , Aimee Avery, Jane Chalker, Mark Kristiansen, Kelly HaupfearJames D. Dalton, Wilda Orisme, Ji Wen, Michael Hubank, Kathreena M Kurian, Catherine Rowe, Stephen P Lowis

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Downloads (Pure)

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 histological review, methylation profiling, custom panel and genome/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 MAP-kinase 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 supports the concept that infant gliomas require a change in diagnostic practice and management.
Original languageEnglish
Number of pages23
JournalCancer Discovery
Early online date1 Apr 2020
DOIs
Publication statusPublished - 12 Jun 2020

Fingerprint

Dive into the research topics of 'Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes'. Together they form a unique fingerprint.

Cite this