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颅外实体瘤（包括神经母细胞瘤、尤文肉瘤和骨肉瘤）是导致儿童发病和死亡的主要恶性肿瘤类型。相比于成人癌症主要由外源性诱变剂或随年龄增长积累的DNA损伤驱动，儿童癌症的发生缺乏长期的突变积累过程。因此，内源性诱变过程可能是诱发儿童致癌突变的主要原因。然而，目前这些肿瘤的发生机制仍不清楚。Gillani等在《Science》上报道称，罕见的种系结构变异（SVs）可能是引起儿童患颅外实体瘤的重要遗传因素。SVs是一类大规模DNA重排，涉及50至数百万个核苷酸的基因组变异。Gillani等的研究结果表明，种系SVs可能导致儿童癌症的早期基因组不稳定，从而促进肿瘤的发生和发展。此外，这一发现有望为靶向治疗策略的制定提供新的思路。

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（图片来源：《Science》）

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