Synchronous Lung Adenocarcinomas With Distinct EGFR Mutations In A Patient With Li-Fraumeni Syndrome

Abstract Li-Fraumeni syndrome (LFS) is a rare autosomal dominant hereditary disorder most frequently caused by pathogenic variants in the TP53 tumor suppressor gene, resulting in impaired regulation of cellular proliferation and apoptosis. Individuals with LFS are predisposed to a spectrum of malignancies affecting multiple organ systems, including the lungs. Lung adenocarcinoma is among the recognized neoplasms that may arise in this population and can be driven by activating mutations in the epidermal growth factor receptor (EGFR) gene. While the coexistence of TP53 and EGFR mutations have been reported, the underlying mechanisms contributing to this association is poorly understood. We present a case of a patient with LFS who developed synchronous bilateral lung adenocarcinomas harboring distinct activating EGFR mutations: L858R point mutation and exon 19 deletion.