OTHR-25 Germline Mutations in Pediatric Brain Tumor

Abstract

Abstract BACKGROUND: The exploration of germline mutations in pediatric brain tumor is helpful to improve the understanding of tumor genesis, guide the treatment, and provide genetic counseling for patients and their families. METHODS: In this study, children with primary brain tumor aged ≤18 years old in Guangdong Sanjiu Brain Hospital were enrolled．Tumor tissue or cerebrospinal fluid (CSF) next-generation sequencing (NGS) tests were required for all included patients. The genetic mutations in these children were analyzed and patients with germline mutations were screened. RESULTS: 135 pediatric patients with NGS detection were included in this patients. 63 patients were medulloblastoma, 54 were glioma. The rest were 5 ependymoma, 2other embryonal tumors, 2 pineoblastoma, 2 germ cell tumors, 1 pituitary adenoma, 1 neuroepithelial tumor, 1 Schwannoma, 1 neuronal tumor, 1 craniopharyngioma and 1 Rosai-Dorfman disease. NGS was performed on tissues of 122 patients and CSF of 13 patients. 7 patients underwent whole exome sequencing and the remaining 115 patients underwent panel detection. 6.67% (9/135) patients took germline mutations, which included 4 gliomas, 3 medulloblastomas, 1 schwannoma and 1 ependymoma. The rate of germline mutations were 7.41% (4/54) and 4.76% (3/63) in gliomas and medulloblastoma, respectively. The germinal mutations included TP53 missense mutation, BLM nonsense mutation, MSH2 nonsense mutation, MSH2 frameshift mutation, SUFU frameshift mutation, FANCI frameshift mutation, SBDS splicing site mutation, NF2 nonsense mutation and DIS3L2 nonsense mutation. These mutations are closely related to with Ligemeni syndrome, Bloom syndrome, Lynch syndrome, nevus basal cell carcinoma syndrome, Fanconi anemia, Shwachman-Diamond syndrome, neurofibromatosis type II and Perlman syndrome, respectively. 2 glioma patients had a family history of cancer. CONCLUSION: Pediatric patients with glioma, medulloblastoma, schwannoma and ependymoma are easily harboring germline mutations. For these patients, a detailed genetic history of family members is required and genetic counseling is recommended.