GOPC-ROS1 fusion due to microdeletion at 6q22 is an oncogenic driver in a subset of pediatric gliomas and glioneuronal tumors

Timothy E. Richardson, Karen Tang, Varshini Vasudevaraja, Jonathan Serrano, Christopher M. William, Kanish Mirchia, Christopher R. Pierson, Jeffrey R. Leonard, Mohamed S. AbdelBaki, Kathleen M. Schieffer, Catherine E. Cottrell, Zulma Tovar-Spinoza, Melanie A. Comito, Daniel R. Bou, George Jour, Matija Snuderl

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1089-1099
Number of pages11
JournalJournal of neuropathology and experimental neurology
Volume78
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • 6q22
  • Astrocytoma
  • Brain tumor
  • GOPC
  • Pediatric glioma
  • ROS1

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