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 (<i>ALK</i>) gene and one novel heterozygous rearrangement Q418Hfs^*11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene <i>FANCD2</i> 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.

神经母细胞瘤与肾母细胞瘤均为儿童常见实体瘤，但二者同步发生的情况极为罕见，且常与综合征相关。本文报道1例特殊病例：一名无先天性畸形或综合征迹象的婴儿，同时罹患神经母细胞瘤与肾母细胞瘤。我们采用下一代测序（next-generation sequencing, NGS）技术，针对94个癌症相关基因及284个单核苷酸多态性（single-nucleotide polymorphism, SNP）位点开展靶向检测，以筛选潜在致病突变基因。研究发现，间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）基因存在1种新型杂合生殖系错义突变p.F58L（c.172T→C）；范可尼贫血基因FANCD2存在1种新型杂合重排Q418Hfs*11（c.1254_1264delins TTACTTAGTACAAGAACTG），可导致截短型蛋白生成。此外，还鉴定出多种与神经母细胞瘤、肾母细胞瘤或多原发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有助于阐明肿瘤发病机制，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。