PATH-19. CLINICAL AND MOLECULAR FEATURES OF GLIOBLASTOMA, IDH-WILDTYPE ARISING IN THE SETTING OF LI FRAUMENI SYNDROME

Abstract

Abstract INTRODUCTION Li Fraumeni Syndrome (LFS) is a rare autosomal dominant tumor predisposition syndrome caused by germline alterations of the TP53. Brain tumors are included in LFS core cancers. Choroid plexus carcinomas and medulloblastomas tend to occur in pediatric LFS patients, while gliomas tend to occur in adult LFS patients. There are few previous reports about gliomas arising in the setting of LFS. Here, we report clinical and molecular features of three cases of glioblastoma, IDH-wildtype arising in the setting of LFS. RESULTS Mean age at diagnosis was 40 years (range: 32-45). Two patients were male. Two patients had medical history of multiple tumors and family history of brain tumors. Magnetic resonance imaging of each patients revealed a left cerebellar peduncle lesion with faint contrast-enhancement, a right parietal lobe lesion with nodular contrast-enhancement and two lesions in the pons (no enhancement) and right parietal lobe (ring enhancement), respectively. All patients underwent chemotherapy including temozolomide and/or bevacizumab combined with radiation therapy (60Gy) after surgery. Mean progression free survival was 10.4 months (range: 5.1-17.0). All patients were admitted to palliative care mean 17.3 months (range: 14.4-21.4) after diagnosis. All patients harbored heterozygous germline mutations of TP53. Whole exome sequencing and copy number analysis of tumor tissues revealed TP53 mutation and PDGFRA amplification in all patients. However, EGFR amplification, the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10-) and mutations of IDH, H3F3A, BRAF and TERT promoter were not detected in all tissues. CONCLUSION We experienced three cases of glioblastoma, IDH-wildtype arising in the setting of LFS. Although tumor locations and radiographic features were varied, all clinical courses were poor. Notably, all tumor tissues harbored TP53 mutation and PDGFRA amplification, while no tumor tissues harbored TERT promoter mutation, EGFR amplification and 7+/10-.