Lineage-Independent Tumors in Bilateral Neuroblastoma.
Lineage-Independent Tumors in Bilateral Neuroblastoma.
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DOI：
10.1056/nejmoa2000962
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发表时间：
2020-11-05
期刊：
影响因子：
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通讯作者：
Behjati S
中科院分区：
文献类型：
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作者：
Coorens THH;Farndon SJ;Mitchell TJ;Jain N;Lee S;Hubank M;Sebire N;Anderson J;Behjati S
儿童肿瘤在不同解剖部位同时发生通常代表转移性疾病。然而，这类肿瘤可以是独立的肿瘤。我们通过对肿瘤和血液之间共有的体细胞突变进行基因分型，研究了两例双侧神经母细胞瘤是否代表两例具有致病性种系突变的儿童的独立肿瘤。我们的结果表明，在这两个孩子中，产生肿瘤的谱系在受精卵的第一次细胞分裂中就分离了，而没有在此之前出现一个常见的癌前克隆。在一名患者中，肿瘤有平行的进化，包括明显的SMARCA4的二次攻击，这是一种被认为是神经母细胞瘤的易感性基因。这些发现表明，双侧神经母细胞瘤具有由种系易感性介导的独立病变。（由英国儿童癌症协会和惠康基金会资助。）
Childhood tumors that occur synchronously in different anatomical sites usually represent metastatic disease. However, such tumors can be independent neoplasms. We investigated whether cases of bilateral neuroblastoma represented independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood. Our results suggested that in both children, the lineages that had given rise to the tumors had segregated within the first cell divisions of the zygote, without being preceded by a common premalignant clone. In one patient, the tumors had parallel evolution, including distinct second hits in SMARCA4, a putative predisposition gene for neuroblastoma. These findings portray cases of bilateral neuroblastoma as having independent lesions mediated by a germline predisposition. (Funded by Children with Cancer UK and Wellcome.)