The Clinical and Molecular Profile of Lung Cancer Patients Harboring the TP53 R337H Germline Variant in a Brazilian Cancer Center: The Possible Mechanism of Carcinogenesis

• Published in: International journal of molecular sciences 2023-10, Vol.24 (20), p.15035
• Main Authors: Lopes, Carlos D. H., Antonacio, Fernanda F., Moraes, Priscila M. G., Asprino, Paula F., Galante, Pedro A. F., Jardim, Denis L., de Macedo, Mariana P., Sandoval, Renata L., Katz, Artur, de Castro, Gilberto, Achatz, Maria Isabel
• Format: Article
• Language: English
• Subjects: Air pollution; Cancer therapies; Carcinogens; Cell cycle; Clinical outcomes; Lung cancer; Mutation; Nervous system; Outdoor air quality; Patients
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242015035

In southern and southeastern Brazil, the TP53 founder variant c.1010G>A (R337H) has been previously documented with a prevalence of 0.3% within the general population and linked to a heightened incidence of lung adenocarcinomas (LUADs). In the present investigation, we cover clinical and molecular characterizations of lung cancer patients from the Brazilian Li-Fraumeni Syndrome Study (BLISS) database. Among the 175 diagnosed malignant neoplasms, 28 (16%) were classified as LUADs, predominantly occurring in females (68%), aged above 50 years, and never-smokers (78.6%). Significantly, LUADs manifested as the initial clinical presentation of Li-Fraumeni Syndrome in 78.6% of cases. Molecular profiling was available for 20 patients, with 14 (70%) revealing EGFR family alterations. In total, 23 alterations in cancer driver genes were identified, comprising 7 actionable mutations and 4 linked to resistance against systemic treatments. In conclusion, the carriers of TP53 R337H demonstrate a predisposition to LUAD development. Furthermore, our results indicate that environmental pollution potentially impacts the carcinogenesis of lung tumors in the carriers of TP53 R337H.