Next-generation sequencing reveals germline mutations in an infant with synchronous occurrence of nephro- and neuroblastoma

Although neuro- and nephroblastoma are common solid tumors in children, the simultaneous occurrence is very rare and is often associated with syndromes. Here, we present a unique case of synchronous occurrence of neuro- and nephroblastoma in an infant with no signs of congenital anomalies or a syndrome. We performed genetic testing for possible candidate genes as underlying mutation using the next-generation sequencing (NGS) approach to target 94 genes and 284 single-nucleotide polymorphisms (SNPs) involved in cancer. We uncovered a novel heterozygous germline missense mutation p.F58L (c.172T→C) in the anaplastic lymphoma kinase (ALK) gene and one novel heterozygous rearrangement Q418Hfs*11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene FANCD2 leading to a truncated protein. Besides, several SNPs associated with the occurrence of neuroblastoma and/or nephroblastoma or multiple primary tumors were identified. The next-generation sequencing approach might in the future be useful not only in understanding tumor etiology but also in recognizing new genetic markers and targets for future personalized therapy.

神经母细胞瘤（neuroblastoma）与肾母细胞瘤（nephroblastoma）均为儿童常见实体肿瘤，但二者同时发生的情况极为罕见，且常伴随综合征发生。本研究报道1例罕见病例：一名无先天性畸形或综合征迹象的婴儿同步罹患神经母细胞瘤与肾母细胞瘤。
我们采用靶向94个癌症相关基因与284个单核苷酸多态性（single-nucleotide polymorphisms, SNPs）位点的下一代测序（next-generation sequencing, NGS）技术，对潜在致病突变的候选基因开展检测。我们在间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）基因中发现1个全新的杂合生殖系错义突变p.F58L（c.172T→C）；同时在范科尼贫血（Fanconi anemia）基因FANCD2中发现1个全新的杂合重排Q418Hfs*11（c.1254_1264delins TTACTTAGTACAAGAACTG），该重排可导致蛋白截短。此外，本研究还鉴定出多个与神经母细胞瘤、肾母细胞瘤或多发原发性肿瘤发生相关的单核苷酸多态性位点。
下一代测序技术未来不仅可用于阐明肿瘤的发病机制，还可用于发掘新型遗传标志物与治疗靶点，为后续个性化治疗提供支撑。