Alterations of genes encoding subunits of the BAF/PBAF complexes are among the most frequent gene aberrations in human cancer. Such alterations have been shown to have an impact on tumor microenvironnement and on the capacity of tumors to respond to immune-checkpoint inhibitors (ICI). We analysed the clinical and genetic data from 43,728 patients accessed through cBioportal. The mutational frequencies of ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1 were 6.6%, 3,4, 3.4, 3.2, 4.1, and 1.2%, respectively. We then investigated the association between the presence of least one nonsynonymous somatic mutation of ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, or SMARCB1 and overall survival of 1661 patients treated with an ICI. Across the entire cohort, patients with BAF/PBAF mutated tumors have a statistically significant improvement in overall survival (median overall survival: 28 months [95% CI 21.6–34.3] versus 15 months [95% CI 12.9–17.0], p < 0.0001). When tumor mutational burden was adjusted for a multivariable Cox regression analysis, BAF/PBAF gene mutations remained an independent prognostic factor for overall survival in patients treated ICI. Our results establish a relationship between mutations in key genes encoding for components of the BAF/PBAF complex and outcome of patients treated with ICI. Further studies are needed to elucidate the underlying mechanisms of this interaction.

中文翻译：

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编码BAF / PBAF复合物成分和免疫检查点抑制剂结果的基因中的失活突变。

编码BAF / PBAF复合物亚基的基因的改变是人类癌症中最常见的基因畸变之一。已经表明这种改变对肿瘤微环境和肿瘤对免疫检查点抑制剂（ICI）的反应能力有影响。我们分析了通过cBioportal访问的43728例患者的临床和遗传数据。ARID1A，ARID1B，ARID2，PBRM1，SMARCA4和SMARCB1的突变频率分别为6.6％，3,4、3.4、3.2、4.1和1.2％。然后，我们调查了ARID1A，ARID1B，ARID2，PBRM1，SMARCA4或SMARCB1的至少一个非同义体细胞突变的存在与使用ICI治疗的1661例患者的总生存率之间的关系。在整个队列中 BAF / PBAF突变的肿瘤患者的总生存期有统计学上的显着改善（中位总生存期：28个月[95％CI 21.6-34.3]与15个月[95％CI 12.9-17.0]，p <0.0001）。当针对多变量Cox回归分析调整了肿瘤突变负荷后，BAF / PBAF基因突变仍然是治疗ICI患者总体生存的独立预后因素。我们的结果建立了编码BAF / PBAF复合物成分的关键基因突变与ICI治疗患者预后之间的关系。需要进一步研究以阐明这种相互作用的潜在机制。BAF / PBAF基因突变仍然是治疗ICI患者总体生存的独立预后因素。我们的结果建立了编码BAF / PBAF复合物成分的关键基因突变与ICI治疗患者预后之间的关系。需要进一步研究以阐明这种相互作用的潜在机制。BAF / PBAF基因突变仍然是治疗ICI患者总体生存的独立预后因素。我们的结果建立了编码BAF / PBAF复合物成分的关键基因突变与ICI治疗患者预后之间的关系。需要进一步研究以阐明这种相互作用的潜在机制。