NGTS-03CHARACTERIZATION OF PRIMARY GLIOMAS IN INDIVIDUALS WITH LI-FRAUMENI SYNDROME: A CASE SERIES

Abstract

Li-Fraumeni Syndrome (LFS) is a rare hereditary cancer syndrome that has classically been associated with familial sarcomas, but now includes brain tumors, premenopausal breast cancer, and adrenocortical carcinomas in its recognized core tumor pathologies. Germline mutations in the TP53 gene are the only known cause of LFS. Affected individuals are typically diagnosed at younger ages than individuals with sporadic tumors and are at risk for multiple malignancies over their lifetime. Characterization of the evolving phenotype of LFS is ongoing, including the use of clinical criteria to identify index patients. Few studies, however, have described the phenotype of primary gliomas in LFS. In this case series, we describe the presentation of four individuals, two male and two female, with primary gliomas and molecularly confirmed LFS at our institution. All individuals presented with high-grade gliomas: two with anaplastic astrocytoma, one with anaplastic oligodendroglioma, and one with glioblastoma multiforme. The age of diagnosis ranged from 25 to 50 years. Glioma was the first presentation of disease in three individuals. The fourth individual had a previous diagnosis of osteosarcoma. Family history was remarkable, positive with regards to Chompret criteria, in two individuals and negative or unknown in two individuals. Molecular tumor testing was available for three individuals: one individual had two somatic TP53 mutations and two individuals had one TP53 mutation with loss of heterozygosity at the opposite allele. These cases demonstrate that individuals with LFS may first present in a neuro-oncology clinic for initial diagnosis. Screening for LFS should be prompted in individuals with a personal and/or family history that includes LFS core tumor pathologies. Further characterization of these individuals is necessary to improve the early identification of LFS, specifically in individuals who present first with glioma, and provide appropriate management recommendations for patients and their families.