Abstract 1837P
Background
Genomic alterations in SWI/SNF chromatin remodeling, which is crucially composed with SMARCA4 and SMARCA2 (BRG1 and BRM; B&B), occur in approximately 16% of solid tumors. Mutations in BRG1 (BRG1m) lead to an expression upregulating of functionally opposite BRM gene, which make BRM as a potential therapeutic target in BRG1m pts. However, the genomic features of B&B in solid tumors remain unclear.
Methods
Based on Genetronhealth Onco Panscan, 14264 Chinese solid tumor pts including lung cancer (LC), brain tumor, colorectal cancer (CRC), gastric cancer (GC), liver cancer, pancreas cancer, soft tissue sarcoma (STS), kidney cancer, breast cancer, urinary tract cancer (UTC) and uterus endometrial cancer (UEC), were retrospectively analyzed.
Results
The frequencies of B&Bm in Chinese solid tumor pts were 3.44% (490/14264) and 1.35% (193/14264), respectively. The most mutated cohorts of BRG1m, percentage-wise, were UTC (12.73%; 14/110), UEC (8.47%; 5/59), GC (5.17%; 34/658), etc. The most in BRMm cohort was UEC (5.08%; 3/59). Previous studies have found that the truncation mutation of BRG1 (tBRG1m) was a poor prognostic factor in multiple solid tumors. Among all pts, the percentage of tBRG1m was 33.27% (163/490), while tBRMm was 16.22% (24/148). Both B&Bm pts featured younger and more males in LC, while the trait was not found in others. Co-mutation analysis found that B&B were mutually exclusive with tumor-driver genes in multi-cancers, such as LC (EGFR, KRAS, ALK), CRC (KRAS), and GC (PIK3CA, ARID1A). In addition, pts harboring B&Bm associated with significantly higher TMB in LC, CRC, GC and STS. Hence, B&B could be served as good predictors of immunotherapy efficacy. Table: 1837P
| Cancer | BRM m TMB | BRG1 m TMB | Unaltered TMB | BRG1 m vs Unaltered | BRM m vs Unaltered |
| LC | 22.13 | 16.54 | 8.23 | <0.001 | <0.001 |
| CRC | 101.20 | 75.33 | 10.35 | <0.001 | <0.001 |
| GC | 54.62 | 27.68 | 9.52 | <0.001 | <0.001 |
| STS | 5.52 | 13.32 | 1.54 | <0.001 | <0.001 |
Conclusions
Above all, this study reveals the genomic features of B&B in Chinese solid tumor pts by NGS. Given the continued development of B&B inhibitors, the systematic exploration of B&Bm provides profound insights of therapeutic strategies for solid tumor pts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.