Theruvath Johanna, Russo Alexandra, Kron Bettina, Paret Claudia, Wingerter Arthur, El Malki Khalifa, Neu Marie A, Alt Francesca, Staatz Gundula, Stein Raimund, Seidmann Larissa, Prawitt Dirk, Faber Jörg
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
b Department of Pediatric Radiology , University Medical Center Mainz , Mainz , Germany.
Pediatr Hematol Oncol. 2016 May;33(4):264-75. doi: 10.1080/08880018.2016.1184362.
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.
虽然神经母细胞瘤和肾母细胞瘤是儿童常见的实体瘤，但同时发生的情况非常罕见，且常与综合征相关。在此，我们报告一例独特的病例，一名婴儿同时发生神经母细胞瘤和肾母细胞瘤，无先天性异常或综合征的迹象。我们采用下一代测序（NGS）方法对94个基因和284个涉及癌症的单核苷酸多态性（SNP）进行靶向检测，以寻找可能作为潜在突变的候选基因。我们在间变性淋巴瘤激酶（ALK）基因中发现了一种新的杂合种系错义突变p.F58L（c.172T→C），在范可尼贫血基因FANCD2中发现了一种新的杂合重排Q418Hfs(*)11（c.1254_1264delins TTACTTAGTACAAGAACTG），导致蛋白质截短。此外，还鉴定了几个与神经母细胞瘤和/或肾母细胞瘤或多种原发性肿瘤发生相关的SNP。下一代测序方法未来可能不仅有助于理解肿瘤病因，还有助于识别新的遗传标记和未来个性化治疗的靶点。
