SUN-283 Impact of Chompret Criteria on the Diagnosis of with Li-Fraumeni Syndrome: Frequency of the TP53 Germline Pathogenic Variant (p.R337H) inTertiary Centers in Brazil

Abstract Disclosure: M.B. Lacerda: None. M. Buchpiguel: None. M. Sousa: None. L. Pimentel: None. L. Leite: None. M.Q. Almeida: None. M. Ferreira: None. M.F. Funari: None. A. Latronico: None. A.O. Hoff: None. B.B. Mendonca: None. M. Diz: None. M. Fragoso: None. Introduction: Li-Fraumeni Syndrome (LFS) is an autosomal dominant hereditary condition caused by pathogenic variants (PVs) in the TP53, which predisposes individuals to early-onset tumors. The germline p.R337H variant is particularly prevalent in Brazil, especially in the South and Southeast regions. Diagnosis is based on the Chompret Criteria {(1. An individual with a tumor belonging to the LFS spectrum before the age of 46 AND At least one first- or second-degree relative with a tumor associated with LFS (except breast cancer if the index case had breast cancer) before the age of 56 OR with multiple tumors OR 2. An individual with multiple tumors (except breast), two of which belong to the LFS spectrum, and the first of them occurred before the age of 46 OR 3. An individual with adrenocortical carcinoma or choroid plexus tumor, regardless of family history.)}. This study evaluates the application of these criteria in LFS. Objective: to analyze clinical and diagnostic data related to TP53 p.R337H variant both retrospectively and prospectively. The secondary objective was to assess the effectiveness of the Chompret Criteria in identifying individuals at increased risk of developing LFS. Subjects and Methods: This study included patients treated at tertiary centers between 2002 and 2024 who met the Chompret Criteria and underwent TP53 gene sequencing. Clinical, epidemiological, and laboratory data were obtained. The study was approved by the local Ethics Committee, and informed consent was obtained. Results: A total of 381 index cases were analyzed. Among these, 107 cases (28%) had TP53 PV, with 77 (72%) identified as carriers of the p.R337H variant. The distribution of Chompret Criteria among p.R337H carriers was as follows: Criterion 1 (25.97%), Criterion 2 (7.79%), and Criterion 3 (66.23%), being the most effective for screening. Carriers of the p.R337H PV were predominantly female (77%), with a mean age of 33 years at diagnosis, and were predominantly from the Southeast region (95%), particularly from the states of São Paulo (79.22%) and Minas Gerais (15.6%). Among p.R337H carriers, the primary tumor sites were adrenal gland (63.52%), breast (23.52%), and soft tissues (7.05%). The most frequent histopathological diagnoses were pediatric adrenal tumors (41.2%), adrenocortical carcinoma (21.2%), and invasive ductal carcinoma of the breast (15.3%). The mortality rate among carriers was 29.9%. Discussion/Conclusion: The Chompret Criteria, particularly Criterion 3, proved highly effective in identifying patients carrying the p.R337H variant. The high prevalence of the p.R337H PV among patients from Southeast Brazil, associated with primary tumors, highlights the need for effective surveillance strategies and early diagnosis, supporting genetic screening in at-risk populations. Presentation: Sunday, July 13, 2025