SUN-281 The Crucial Role of the TP53 Carrier Gene in Human Tumorigenesis: Implications for Cancer Screening

Abstract Disclosure: M.C. Fragoso: None. M. Sousa: None. M. Lacerda: None. M. Buchpiguel: None. M. Almeida: None. A. Latronico: None. B. Mendonça: None. D. Di Matteo: None. W. Lins: None. M. Jatene: None. Introduction: Li-Fraumeni Syndrome (LFS) is an autosomal dominant disorder caused by pathogenic variants (PV) in TP53, encoding a transcription factor critical for tumor suppression. Around 20% of LFS families carry one of six hotspot PVs (p.R175H, p.G245S, p.R248Q, p.R248W, p.R273H, p.R282W). TP53 variants influence disease penetrance, cancer predisposition, and secondary malignancy risk. Common tumors include adrenocortical carcinoma, soft tissue sarcomas, and bone tumors. The clinical and genetic aspects of this syndrome predispose individuals to develop multiple types of cancer at an early age. Given the severity and associated risks, a panel of experts recommends that all individuals with a confirmed clinical or molecular diagnosis undergo strict surveillance. Early screening using the Toronto Protocol is essential for detecting and intervening in malignancies at initial stages. To illustrate the clinical impact of PV in TP53 and surveillance importance, we report a pediatric case. Case Report: A 5-year-old boy with a significant family history of cancer in close relatives before the age of 45 was diagnosed with LFS. Genetic analysis revealed c.818G>A (p.Arg273H), a heterozygous variant in exon 8. The child had no gestational or perinatal complications. To date, no signs or symptoms of hormonal hyperfunction have been observed. Systematic screening for syndrome-associated malignancies was initiated using imaging studies, including annual Magnetic Resonance Imaging (MRI) of the chest, abdomen, pelvis, and brain. In February 2023, a chest MRI revealed a 2.5 cm nodule on the right side. PET-FDG imaging identified a nodular lesion with increased uptake, with a metabolic size of 6.7 × 4.6 × 4.2 cm, to the right of the midline (SUVmax: 6,8). A thymus biopsy via radiointervention confirmed a type B1 thymoma, leading to an initial decision for surveillance. In July, a follow-up MRI showed a heterogeneous solid mass with cystic areas and no contrast enhancement, measuring 5.5 × 4.5 × 3.7 cm in the anterior mediastinum, paracardiac on the right. This mass showed a significant increase in size within just five months and was not detected in a previous examination in 2021, surgical excision was performed. Histopathological analysis confirmed thymic carcinoma. Conclusion: LFS plays a crucial role in the pathogenesis of pediatric cancers, with PV in TP53 being associated with an increased predisposition to aggressive tumors with a poorer prognosis. Although the relationship between thymic tumors and pathogenic TP53 changes is rare, particularly in pediatric populations, surgical resection is a fundamental therapeutic approach for controlling neoplasms linked to the syndrome. This case highlights the importance of genetic and imaging screening in timely detection and management of malignancies in LFS patients. Presentation: Sunday, July 13, 2025