GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors.
Adaptor Proteins, Signal Transducing
/ genetics
Brain
/ pathology
Brain Neoplasms
/ genetics
Carcinogenesis
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 6
/ genetics
DNA Methylation
Epigenesis, Genetic
Female
Glioma
/ genetics
Golgi Matrix Proteins
/ genetics
Humans
Male
Oncogene Proteins, Fusion
/ genetics
Protein-Tyrosine Kinases
/ genetics
Proto-Oncogene Mas
Proto-Oncogene Proteins
/ genetics
6q22
Astrocytoma
Brain tumor
GOPC
Pediatric glioma
ROS1
Journal
Journal of neuropathology and experimental neurology
ISSN: 1554-6578
Titre abrégé: J Neuropathol Exp Neurol
Pays: England
ID NLM: 2985192R
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
pubmed:
19
10
2019
medline:
18
6
2020
entrez:
19
10
2019
Statut:
ppublish
Résumé
ROS1 is a transmembrane receptor tyrosine kinase proto-oncogene that has been shown to have rearrangements with several genes in glioblastoma and other neoplasms, including intrachromosomal fusion with GOPC due to microdeletions at 6q22.1. ROS1 fusion events are important findings in these tumors, as they are potentially targetable alterations with newer tyrosine kinase inhibitors; however, whether these tumors represent a distinct entity remains unknown. In this report, we identify 3 cases of unusual pediatric glioma with GOPC-ROS1 fusion. We reviewed the clinical history, radiologic and histologic features, performed methylation analysis, whole genome copy number profiling, and next generation sequencing analysis for the detection of oncogenic mutation and fusion events to fully characterize the genetic and epigenetic alterations present in these tumors. Two of 3 tumors showed pilocytic features with focal expression of synaptophysin staining and variable high-grade histologic features; the third tumor aligned best with glioblastoma and showed no evidence of neuronal differentiation. Copy number profiling revealed chromosome 6q22 microdeletions corresponding to the GOPC-ROS1 fusion in all 3 cases and methylation profiling showed that the tumors did not cluster together as a single entity or within known methylation classes by t-Distributed Stochastic Neighbor Embedding.
Identifiants
pubmed: 31626289
pii: 5593615
doi: 10.1093/jnen/nlz093
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
GOPC protein, human
0
Golgi Matrix Proteins
0
MAS1 protein, human
0
Oncogene Proteins, Fusion
0
Proto-Oncogene Mas
0
Proto-Oncogene Proteins
0
Protein-Tyrosine Kinases
EC 2.7.10.1
ROS1 protein, human
EC 2.7.10.1
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1089-1099Informations de copyright
© 2019 American Association of Neuropathologists, Inc. All rights reserved.