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

ABSTRACT

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.

KEYWORDS:

• ALK
• FANCD2
• nephroblastoma
• neuroblastoma
• next-generation sequencing
• predisposing genetic alterations
• wilms tumor

Acknowledgments

We thank Norbert Graf and Nasenien Nourkami-Tutdibi from the SIOP2001/GPOH nephroblastoma study group as well as Barbara Hero and Frank Berthold from the neuroblastoma NB 2004 study group for their valuable participation in discussing a consensus diagnostic and therapeutic strategy. Furthermore, we like to thank Lea Roth for her excellent technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.