PATH-48. FUSION TESTING IN ADULT VERSUS PEDIATRIC LOW AND HIGH GRADE BRAIN TUMORS FOR ELIGIBILITY FOR TRIALS. (5th November 2018)

• Record Type: Journal Article
• Authors: Ormond, David; Damek, Denise; Willard, Nicholas; Ewalt, Mark; Kleinschmidt-DeMasters, Bette
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi169
• Page End: vi169
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.702
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Since January 2017, our molecular laboratory has assessed 47 pediatric and 23 adult primary brain tumors for fusions that might result in novel treatment; adults with glioblastoma (GBM) had been screened specifically for the STARTRK-2 study. This trial has open arms for patients whose tumors demonstrate ROS1, ALK, or NTRK 1/2/3 fusions. We now review our results in pediatric versus adults. MATERIALS AND METHODS: Fusion analysis was performed with the Archer FUSIONPlex Solid Tumor Kit, 1/2017-5/2018. RESULTS: 18 adults with GBMs (17/18 IDH-wildtype) screened for the STARTRK-2 study were negative for fusions or potentially oncogenic transcripts in ALK, ROS1 or MET. However, one adult IDH-wildtype GBM showed a FGFR3-TACC3 actionable fusion that might allow erdafitinib therapy. Three more were found to have fusions of uncertain significance: an IDH-wildtype GBM with EGFR-SEPT14 fusion, an IDH-wildtype GBM with EGFR-PSPH fusion, and the sole IDH-mutant GBM with ZMIZ1-FGFR2 fusion transcript. 5 additional adults were screened for BRAF V600E mutation / BRAF-KIAA1549 fusion, of which 1 fusion and 1 mutation was identified. 42 pediatric patients with low-grade glial/glioneuronal tumors were assessed: 10 had mutation and 5 fusion, potentially allowing for BRAF or MEK inhibitors. Actionable fusions for potential trial entry were found in a 6-year-old male with pilocytic astrocytoma (PA) (GOPC-ROS1 fusion), a 4 month-old male with congenital GBM (MZT2B-ALK fusion), and a 3 year-old female with epithelioid GBM (ETV6-NTRK3 fusion). FGFR1-TACC1 fusions were found in three pediatric patients (16-year-old female with PA, 9-year-old male with extraventricular neurocytoma, 1-year-old male with spinal cord PA). CONCLUSIONS: Actionable fusions can be found in both adult and pediatric patients, although STARTRK-2 study entry criteria were not met in any of the 18 adults. The most unusual fusions thus far have been the congenital GBM (MZT2B-ALKfusion) and the epithelioid GBM (ETV6-NTRK3 fusion).