202002,Tokunaga

研究発表を行った学会；55th Annual Meeting of the American Society of Clinical Oncology (ASCO 2019)
2019年 5月31日〜6月4日（Chicago）
タイトル； Gene mutations of SWI/SNF complex and molecular profile in colorectal cancer.
発表者；徳永 竜馬氏
（熊本大学　大学院生命科学研究部　消化器外科学教室）
要旨；
Background: The SWI/SNF complex includes proteins produced by 29 genes that regulate chromatin structure remodeling through effects upon transcription, replication, and repair. Understanding how SWI/SNF gene mutations interact to affect cancer progression could lead to new treatment strategies.
Methods: We analyzed 7,370 colorectal cancer (CRC) samples with immunohistochemical stains (IHC) and Next-Generation Sequencing (NGS) using a 592-gene panel to examine the association between gene mutations of the SWI/SNF complex (ARID1A, ARID2, PBRM1, SMARCA4, SMARCB1, SMARCE1, BCL11A, BCL11B, BCL7A, SS18, and SS18L1) and molecular features.
Results: The overall mutation rate of the SWI/SNF complex genes was 11.3% (ARID1A: 7.7%, ARID2: 1.7%, SMARCA4: 1.3%, PBRM1: 1.2%, BCL11A: 1.0%, SMARCB1: 0.5%, BCL11B: 0.5%, SMARCE1: 0.3%, SS18: 0.3%, BCL7A: 0.1%, SS18L1: 0.1%). When compared to tumors with SWI/SNF wild-type genes, those tumors with SWI/SNF gene mutations showed significantly higher rates of microsatellite instability (MSI)-high (40.9% vs 2.4%, P < 0.001), tumor mutational burden (TMB)-high (>= 10mut/MB) (56.8% vs 21.6%, P < 0.001) and PD-L1 positivity (17.9% vs 5.5%, P < 0.001). Tumors with each gene mutant also had strong association with the immune profile (MSI-high, TMB-high, and PD-L1 positivity). Furthermore, even SWI/SNF gene mutant samples with microsatellite stable status were significantly associated with TMB-high (28.2%, P < 0.001) and PD-L1 positivity (10.0%, P < 0.001).
Conclusions: Gene mutations of the SWI/SNF complex exhibit findings that suggest that this subgroup of CRCs may have a higher likelihood of response to PD-1 and PD-L1 targeting monoclonal antibodies. If validated in other data sets, these findings can be used to justify clinical trials with eligibility based upon the presence of mutations within the SWI/SNF complex.