Epen-12. Novel Ptch1-inppl1 Fusion in a Patient With Extraneural Metastatic Ependymoma - a Case Report
Year: 2018
Type: article
Study design: Case Report
Abstract: Extraneural metastatic spread of ependymoma is rare, and associated molecular genetic drivers are unknown. We report a 6 year-old male diagnosed with a right fronto-parietal tumor who underwent gross total resection in February, 2015. Pathology revealed anaplastic ependymoma and FISH was positive for RELA fusion. The patient received adjuvant proton beam radiation therapy. He developed locally recurrent disease with spinal metastasis at T8 level in May, 2016 and subsequent treatment included surgery, focal radiotherapy, everolimus and craniospinal irradiation. He received nivolumab for further disease progression, beginning in July, 2017. One week after treatment initiation, he was noted to have increasing abdominal girth, and CT abdomen and pelvis revealed liver, omental, and pleural based disease, which were confirmed to be metastatic ependymoma on biopsy. We performed next generation sequencing using MSK-IMPACTTM (Integrated Mutation Profiling of Actionable Cancer Targets) on samples for the primary and recurrent brain tumor, as well as metastatic disease. In the metastatic sample only, we identified a novel acquired t(9;11) translocation resulting in a PTCH1-INPPL1 fusion, t(9;11)(q22.32;q13.4)(chr9:g.98211830::chr11:g.71941318) with PTCH1 exons 1–21 fused with INPPL1 exons 10–28. Treatment with vismodegib was attempted, but not tolerated by the patient due to advanced disease. Our data suggests that inactivation of PTCH1 may drive extraneural metastasis of ependymoma, providing a target for molecular targeted therapy using sonic hedgehog pathway inhibitors. A patient derived xenograft from this patient’s tumor is pending confirmation of engraftment, and should provide opportunities for functional validation and therapeutic testing of the novel PTCH1-INPPL1 fusion.
Source: Neuro-Oncology
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2809550662