case_images: PMC11788012_01
case_images: Clinical data of NSCLC case with EGFR/TP53/CUL3 triple mutation. (A) Chest computed tomography (CT) revealed a 16 mm x 11 mm nodule in the left lower lung lobe. (B) Positron-emission tomography-CT revealed liver metastasis, bone metastasis, and left adrenal metastasis. (C) Brain magnetic resonance imaging revealed multiple brain metastases. (D) Visual summary of the patient's clinical course. NSCLC, non-small cell lung cancer, EGFR: Epidermal growth factor receptor, TP53: Tumor protein p53, CUL3: Cullin 3, DIC: Disseminated intravascular coagulation, CBDCA: Carboplatin, PEM: Pemetrexed, DTX: Docetaxel, Plt: Platelet.
case_images: TCA-16-e15523-g002.jpg
case_images: PMC11788012_01_TCA-16-e15523-g002.jpg
case_images: tca15523-fig-0001
case_images: Chest computed tomography (CT) revealed a nodule (Figure 1A) in the left lower lung lobe, multiple pulmonary metastases, enlargement of mediastinal lymph nodes, and pericardial effusion. Positron-emission tomography-CT revealed liver metastasis, large numbers of bone metastases, and left adrenal metastasis (Figure 1B), and brain magnetic resonance imaging revealed multiple brain metastases (Figure 1C). She passed away 23 months after the initiation of osimertinib (Figure 1D).
case_images: Frequencies of EGFR, TP53, and CUL3 mutations among patients with non-small cell carcinoma in the GENIE cohort v15.1-public database. Among patients with EGFR mutations, 1992 had an EGFR mutation without TP53 or CUL3 mutations, 2316 had EGFR/TP53 double mutations, and 18 had EGFR/TP53/CUL3 triple mutations. EGFR: Epidermal growth factor receptor, TP53: Tumor protein p53, CUL3: Cullin 3, GENIE: Genomics, Evidence, Neoplasia, Information, Exchange.
case_images: TCA-16-e15523-g001.jpg
case_images: PMC11788012_01_TCA-16-e15523-g001.jpg
case_images: tca15523-fig-0002
case_images: Overall, 1992 had only EGFR mutations (46.0%), 2316 had EGFR/TP53 double mutations (53.4%), and 18 had EGFR/TP53/CUL3 triple mutations (0.4%) (Figure 2).
case_images: Kaplan-Meier curves of overall survival, comparing EGFR, EGFR/TP53, and EGFR/TP53/CUL3 mutations. The EGFR/TP53/CUL3 triple mutation yielded a worse prognosis than the EGFR single mutation (HR: 2.65, 95% CI: 1.37-5.12, p = 0.004) and appeared to yield a worse prognosis than the EGFR/TP53 double mutation (HR: 1.30, 95% CI: 0.68-2.51), although the difference was not statistically significant (p = 0.43). The median OS was 84.0 (EGFR), 42.2 (EGFR/TP53), and 32.6 (EGFR/TP53/CUL3) months. EGFR: Epidermal growth factor receptor, TP53: Tumor protein p53, CUL3: Cullin 3, HR: Hazard ratio, 95% CI: 95% confidence interval, OS: Overall survival.
case_images: TCA-16-e15523-g004.jpg
case_images: PMC11788012_01_TCA-16-e15523-g004.jpg
case_images: tca15523-fig-0003
case_images: It also seemed to yield a worse prognosis than the EGFR/TP53 double mutation (HR: 1.30, 95% CI: 0.68-2.51), although the difference was not significant (p = 0.43) (Figure 3).