Analysis of sporadic neuroblastic tumors reveals a novel PHOX2B mutation in neuroblastoma

Germline mutations of PHOX2B have been associated with neurocristopathies predisposing to neuroblastoma (NB). Genetic studies on NB have also shown that PHOX2B is rarely mutated in both sporadic and hereditary NB cases. In this study, we aimed to further evaluate the mutational status of PHOX2B in 120 additional neuroblastic tumors. Genomic DNA samples were isolated from tumor tissues of 104 neuroblastoma, 9 ganglioneuroblastoma, and 7 ganglioneuroma cases. Mutation analysis by direct sequencing of all PHOX2B exons revealed a novel missense mutation of c. 94G > A (D32N) in exon 1 in an NB case. In addition, indel variations of c. 1101_1118het-del18 and c. 1098_1136het-del39 in exon 3 that encodes the second polyalanine tract were detected in an NB and a ganglioneuroma, respectively. Two different single nucleotide polymorphisms, c. 552C > T and c. 762A > C were found in five NB samples. Polyphen analysis revealed that the amino acid substitution due to the c. 94G > A novel missense mutation is in the highly conserved residue among phylogenetically distant species and it has potentially a disease-causing effect