e21668 Background: RB1 is one of the most vital cancer suppressor genes in various cancer types. RB1 mutation always occurs in treatment-naïve small cell lung cancer (SCLC) patients or in resistance to EGFR TKI therapy of non-small cell lung cancer (NSCLC) patients. However, we observed a group of clinical NSCLC patients, and found that RB1 mutations also occurred in treatment-naïve patients. Methods: RB1 is one of the most vital cancer suppressor genes in various cancer types. RB1 mutation always occurs in treatment-naïve small cell lung cancer (SCLC) patients or in resistance to EGFR TKI therapy of non-small cell lung cancer (NSCLC) patients. However, we observed a group of clinical NSCLC patients, and found that RB1 mutations also occurred in treatment-naïve patients. Results: Nonsense and frame-shift mutations were the major pathogenic mutations found in RB1 gene, which predicted RB1 protein-deficient in these mutational patients. Furthermore, we found these RB1 mutation patients had TP53 mutations at the same time. Patients with RB1 mutation had a higher smoking prevalence than patients who had wildtype RB1 genes (P < 0.0001). Gene testing showed RB1 mutations patients also developed EGFR driver mutations, while the mutation frequency was significantly lower than RB1 wildtype patients ( P = 0.0368). Eight RB1 mutated patients diagnosed with actionable EGFR mutations, including exon 19 del, L858R, L861Q, G719S and S768I, while no patients diagnosed with EGFR exon 20 insertion. 10 (62.5%, 10/16) patients in RB1 mutated group, and 25(32.1%, 25/78) patients with RB1 wildtype had bone metastases. The proportion of bone metastases in patients with RB1 mutation was significantly increased than others ( P = 0.0216). Conclusions: This study demonstrates that the function of tumor suppressor gene RB1 in advanced stage of NSCLC. From the results, we considered RB1 mutation had influence on bone metastases. Although loss-of-function mutations in tumor suppressor gene (TSG) RB1 always had no targets therapeutic drugs, it also suggested that some other clinically treatment can be performed as soon as possible.
Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer
