Relationship between loss-of-function mutation of the stromal antigen 2 gene and treatment in non-small cell lung cancer.

Abstract

e20509 Background: The protein encoded by Stromal Antigen 2 ( STAG2) gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Loss-of-function (LOF) mutations of STAG2 gene are commonly detected in different tumors including non-small-cell lung cancer. However, there is no relevant research on the impact of STAG2 alterations on lung cancer treatment. Here we explored the correlation between the LOF of STAG2 and clinical features, concomitant genetic alterations and treatment in NSCLC pts. Methods: A total of 2882 NSCLC pts were enrolled. All the tissue samples were detected by DNA based next generation sequencing (NGS) with a 1021 gene panel. Clinical information was obtained synchronously from physicians and surgeons. According to whether LOF of STAG2 is detected, pts were divided into LOF subgroup and wild type (WT) group. Results: All pts enrolled are Chinese, and median age at diagnosis of them is 63±11.21. Compared to the WT subgroup, a higher average TMB was observed in the LOF group (12.64muts/Mb vs. 6.66mut/Mb, P＜0.05). Between the LOF group and the WT group, there were no significantly difference in all clinical baseline characteristics including age at diagnosis, gender, tumor stage and pathological type. At the time of sample collection, there was no significant difference between the two groups of pts whether they had received systemic treatment (chemotherapy, targeted therapy or immunotherapy) and systemic treatment, and the number of systemic treatment lines received. Neither significant differences in driver gene alteration and other accompanying mutations were observed in the two groups. Conclusions: In NSCLC pts, LOF of STAG2 is not a change after drug resistance, but it may lead to an increase in TMB, which indicates that these pts may have more benefits from immunotherapy. But the influence on prognosis of NSCLC pts needs further research to clarify.