Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Fam Cancer. 2010 Sep;9(3):425-30. doi: 10.1007/s10689-009-9319-8.
Wilms tumor and neuroblastoma are childhood tumors of the kidney and undifferentiated neural crest cells, respectively. Both disorders are primarily sporadic, but familial Wilms tumor pedigrees and familial neuroblastoma pedigrees are each well recognized and account for approximately 1-3% of each tumor type. Families with Wilms tumor and neuroblastoma in the same, or related individuals, have not been reported. Here, we present nine families with two or more individuals with Wilms tumor and/or neuroblastoma. The affected individuals were otherwise well, without syndromic features. Although this co-occurrence might be due to chance in some families, the coexistence of two rare embryonal tumors in related individuals of multiple families suggests an underlying genetic susceptibility to both tumors. We undertook mutational analysis of the genes known to predispose to non-syndromic familial Wilms tumor (WT1) or neuroblastoma (PHOX2B, ALK) which excluded these as the underlying predisposition genes in the nine families. We also excluded epigenetic and copy-number abnormalities at 11p15 which are known to predispose to embryonal tumors including Wilms tumor and neuroblastoma. Overall, these data suggest that families with both Wilms tumor and neuroblastoma represent a previously unrecognized familial cancer syndrome in which the underlying predisposition gene(s) remain to be determined.
Wilms 瘤和神经母细胞瘤分别是儿童肾脏和未分化神经嵴细胞的肿瘤。这两种疾病主要都是散发性的，但家族性 Wilms 瘤家系和家族性神经母细胞瘤家系是众所周知的，分别占每种肿瘤类型的约 1-3%。在同一家庭或相关个体中同时患有 Wilms 瘤和神经母细胞瘤的家族尚未报道。在这里，我们介绍了 9 个有两个或更多个体患有 Wilms 瘤和/或神经母细胞瘤的家庭。受影响的个体情况良好，没有综合征特征。虽然这种同时发生在某些家庭中可能是偶然的，但多个家族中相关个体中两种罕见的胚胎性肿瘤的共存表明存在两种肿瘤的潜在遗传易感性。我们对已知易患非综合征性家族性 Wilms 瘤（WT1）或神经母细胞瘤（PHOX2B、ALK）的基因进行了突变分析，排除了这些基因作为 9 个家庭中潜在的易患基因。我们还排除了已知易患包括 Wilms 瘤和神经母细胞瘤在内的胚胎性肿瘤的 11p15 上的表观遗传和拷贝数异常。总的来说，这些数据表明，同时患有 Wilms 瘤和神经母细胞瘤的家庭代表了一种以前未被认识到的家族性癌症综合征，其潜在的易患基因仍有待确定。
