High prevalence of EGFR mutations in lung adenocarcinomas from Brazilian patients harboring the TP53 p.R337H variant

Abstract Background Lung cancer represents around 3.6% of all Li-Fraumeni Syndrome (LFS)-associated tumors. A high prevalence of p.R337H germline mutation in the TP53 gene has been observed in Brazil and family histories of cancer associated with this variant range from isolated cases to families fulfilling Li-Fraumeni-like or Li-Fraumeni criteria. We aimed to evaluate the frequency of EGFR mutations in lung adenocarcinoma (LA) diagnosed in Brazilian patients carrying the TP53 founder mutation p.R337H, as well as the frequency of TP53 p.R337H mutation among LA cases with EGFR mutation. Methods Patients diagnosed with LA were selected from a total of 164 TP53 p.R337H mutation carriers followed at A.C. Camargo Cancer Center. Tumor samples were submitted to EGFR hotspot mutations sequencing. TP53 p.R337H was genotyped in a cohort of 257 LA tumor samples, 114 with and 143 without EGFR activating mutations. Sequencing was performed using Ion Torrent. Results The frequency of LA among TP53 p.R337H carriers was 5.4% (9/164), and EGFR mutations were detected in 89% (8/9) of these patients. The prevalence of TP53 variants at codon 337 in patients with LA harboring EGFR activating mutations was 5.3% (6/114 – 5 p.R337H and 1 p.R337C) and 12.5% (4/32) in LA tumors diagnosed at any age and before the age of 50 years, respectively. This prevalence was significantly higher than that in the cohort of LA tumors with no EGFR activating mutation (1/143 in LA diagnosed at any age, 0/34 in LA diagnosed before the age of 50 years). Conclusions There is a higher than expected frequency of EGFR activating mutations in LA Brazilian patients with TP53 p.R337H mutation. The high frequency of p.R337H/C carriers among patients with EGFR-mutated LA indicates that TP53 genetic testing should be recommended to these patients, regardless of whether they fulfill LFS/LFL criteria or no defined cancer risk criteria.