ROS1-GOPC gene fusion characterizes a minor subset of brain tumors

Document Type

Article

Publication Date

6-1-2020

Publication Title

Cancer Genetics

Abstract

Brain tumors are the leading cause of cancer-related death in children and young adults. Molecular genetic/genomic characteristics subclassify brain tumors, which associate with different outcomes and identify pathways for therapeutic options. We present four new glial brain tumors with ROS1-GOPC gene fusion. Only 14 brain tumors with this variant, 7 adult and 7 pediatric, are published. Our tumors from 3 pediatric and one young adult were discovered by SNP microarray; confirmed by FISH or sequencing-based testing. Reviewing data, we find that age at diagnosis ranged from congenital to 8th decade with pediatric cases 0-8 years. Most tumors with ROS1-GOPC fusion arise in midline brain structures, often thalamus and basal ganglia. Histopathological characterization is heterogeneous; tumor grade varied from low grade gliomas NOS to Grade IV glioblastoma (GBM). Microscopic descriptions often indicate different cell populations or regions with different morphologic characteristics. Ki67, a measure of proliferative activity, ranged from 1% to 40%. Chromosome analysis is reported in one tumor and available for two of our tumors. Recurrent loss of chromosome 1/1p, 5q, and 22 and gain of 5p, 8, 16, 20, and 7 is noted. Publicly available data from ROS1-GOPC positive tumors shows recurrent CDKN2A/B deletions, mutations of PTEN and TP53. Of 11 pediatric/young adult patients for which outcome information is available, 10 remain alive at time of report. ROS1 rearrangement in non-small-cell lung cancers is targetable with the newer generation ROS1 inhibitors. ROS1 fusions in primary brain tumors may also be responsive to clinical intervention with kinase inhibitors.

Volume

244

First Page

3

DOI

10.1016/j.cancergen.2020.04.011

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