BACKGROUND The SWI/SNF complex is an important chromatin remodeler, commonly dysregulated in cancer, with an estimated mutation frequency of 20%. ARID1A is the most frequently mutated subunit gene. Almost nothing is known about the other familiar members of the SWI/SNF complexes, SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1), in oesophageal adenocarcinoma (EAC). METHODS We analysed a large cohort of 685 patients with EAC. We used four different antibodies to detect a loss-of-protein of ARID1A BRM, BRG1 and INI1 by immunohistochemistry and correlated these findings with molecular and clinical data. RESULTS Loss of ARID1A, BRG1, BRM and INI1 was observed in 10.4, 3.4, 9.9 and 2% of EAC. We found a co-existing protein loss of ARID1A and BRM in 9.9% and of ARID1A and BRG1 in 2.2%. Patients with loss of ARID1A and TP53 wildtype EACs showed a shortened overall survival compared with AIRDA1A-positive tumours [median overall survival was 60.1 months (95%CI 1.2-139.9 months)] in patients with ARIDA-1A expression and 26.2 months (95%CI 3.7-19.1 months) in cases of ARIDA-1A loss (p = 0.044). Tumours with loss or expression of ARID1A and TP53 loss were not associated with a difference in survival. Only one tumour revealed high microsatellite instability (MSI-H) with concomitant ARID1A loss. All other ARID1A loss-EACs were microsatellite-stable (MSS). No predictive relevance was seen for SWI/SNF-complex alterations and simultaneous amplification of different genes (PIK3CA, KRAS, c-MYC, MET, GATA6, ERBB2). CONCLUSION Our work describes, for the first time, loss of one of the SWI/SNF ATPase subunit proteins in a large number of adenocarcinomas of the oesophagus. Several papers discuss possible therapeutic interventions for tumours showing a loss of function of the SWI/SNF complex, such as PARP inhibitors or PI3K and AKT inhibitors. Future studies will be needed to show whether SWI/SNF complex-deficient EACs may benefit from personalized therapy.

中文翻译：

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食管腺癌中SWI / SNF-ATPase亚基成员SMARCF1（ARID1A），SMARCA2（BRM），SMARCA4（BRG1）和SMARCB1（INI1）的丢失。

背景SWI / SNF复合物是一种重要的染色质重塑剂，通常在癌症中失调，估计突变频率为20％。ARID1A是最频繁突变的亚基基因。关于食管腺癌（EAC）中SWI / SNF复合物的其他熟悉成员SMARCA2（BRM），SMARCA4（BRG1）和SMARCB1（INI1）几乎一无所知。方法我们分析了685名EAC患者的大队列。我们使用了四种不同的抗体通过免疫组织化学检测ARID1A BRM，BRG1和INI1的蛋白质损失，并将这些发现与分子和临床数据相关联。结果在10.4％，3.4％，9.9％和2％的EAC中观察到了ARID1A，BRG1，BRM和INI1的丢失。我们发现ARID1A和BRM的蛋白质损失共存9.9％，而ARID1A和BRG1的蛋白质损失共2.2％。与AIRDA1A阳性肿瘤相比，ARID1A和TP53野生型EAC缺失的患者显示出总体生存期缩短[ARIDA-1A表达患者的中位总体生存期为60.1个月（95％CI为1.2-139.9个月）]，而AIRDA1A表达阳性的患者为26.2个月（95％） ARIDA-1A丢失的情况下，CI为3.7-19.1个月（p = 0.044）。丢失或ARID1A和TP53表达缺失的肿瘤与生存率差异无关。只有一个肿瘤显示出高微卫星不稳定性（MSI-H）并伴有ARID1A丢失。所有其他ARID1A损失EAC都是微卫星稳定（MSS）。没有观察到SWI / SNF复合物改变和同时扩增不同基因（PIK3CA，KRAS，c-MYC，MET，GATA6，ERBB2）的预测相关性。结论我们的工作首次描述了 大量食道腺癌中一种SWI / SNF ATPase亚基蛋白的缺失 几篇论文讨论了显示SWI / SNF复合体功能丧失的肿瘤的可能治疗手段，例如PARP抑制剂或PI3K和AKT抑制剂。需要进行进一步的研究以显示SWI / SNF复合体缺陷型EAC是否可以从个性化治疗中受益。