Whole genome and transcriptome sequencing of a cohort of 67 leiomyosarcomas revealed ATRX to be one of the most frequently mutated genes in leiomyosarcomas after TP53 and RB1. While its function is well described in the alternative lengthening of telomeres mechanism, we wondered whether its alteration could have complementary effects on sarcoma oncogenesis. ATRX alteration is associated with the down-expression of genes linked to differentiation in leiomyosarcomas, and to immunity in an additional cohort of 60 poorly differentiated sarcomas. In vitro and in vivo models showed that ATRX loss increases tumor growth rate and immune escape by decreasing the immunity load of active mast cells in sarcoma tumors. These data indicate that an alternative to unsuccessful targeting of the adaptive immune system in sarcoma could be to target the innate system. This might lead to a better outcome for sarcoma patients in terms of ATRX status.

中文翻译：

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ATRX改变有助于多形性肉瘤中的肿瘤生长和免疫逃逸

一组67个平滑肌肉瘤的全基因组和转录组测序表明，ATRX是继TP53和RB1之后在平滑肌肉瘤中最频繁突变的基因之一。虽然其功能在端粒机制的替代性延长过程中得到了很好的描述，但我们想知道其改变是否可能对肉瘤的发生具有互补作用。ATRX改变与平滑肌肉瘤中分化相关基因的下表达有关，并与另外60个低分化肉瘤中的免疫相关。体外和体内模型表明，ATRX丢失通过降低肉瘤肿瘤中活性肥大细胞的免疫负荷而增加了肿瘤生长速率和免疫逃逸。这些数据表明，肉瘤中适应性免疫系统无法成功靶向的另一种选择可能是靶向先天系统。