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

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Cancer Genetics


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.



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