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.
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Johanna
J
Theruvath
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Alexandra
A
Russo
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Bettina
B
Kron
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Claudia
C
Paret
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Arthur
A
Wingerter
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Khalifa
K
El Malki
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Marie A
MA
Neu
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Francesca
F
Alt
b Department of Pediatric Radiology , University Medical Center Mainz , Mainz , Germany.
Gundula
G
Staatz
c Department of Pediatric Urology , University Medical Center Mainz , Mainz , Germany.
Raimund
R
Stein
d Department of Pediatric Pathology , University Medical Center Mainz , Mainz , Germany.
Larissa
L
Seidmann
e Department of Molecular Pediatrics , Center for Pediatrics and Adolescent Medicine , University Medical Center Mainz , Mainz , Germany.
Dirk
D
Prawitt
a Department of Pediatric Hematology/Oncology , University Medical Center Mainz , Mainz , Germany.
Jörg
J
Faber
D000077548:Anaplastic Lymphoma Kinase; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics* / Q000628:therapy; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000628:therapy; D009447:Neuroblastoma / Q000235:genetics* / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics* / Q000628:therapy
C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
ALK; FANCD2; nephroblastoma; neuroblastoma; next-generation sequencing; predisposing genetic alterations; wilms tumor