Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis

Abstract

To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated using immunohistochemical analysis in 259 samples. Based on genetic alterations, the following 6 subgroups were identified: groups A (<i>ALK</i> abnormalities), B (other gene mutations), C (<i>MYCN</i> amplification), D (11q loss of heterozygosity [LOH]), E (at least 1 copy number variants), and F (no genetic changes). Groups A to D showed advanced disease and poor prognosis, whereas groups E and F showed excellent prognosis. Intriguingly, in group A, <i>MYCN</i> amplification was not a significant prognostic marker, while high ALK expression was a relevant indicator for prognosis (<i>P</i> = 0.033). Notably, the co-existence of <i>MYCN</i> amplification and 1p LOH, and the co-deletion of 3p and 11q were significant predictors of relapse (<i>P</i> = 0.043 and <i>P</i> = 0.040). Additionally, 6q/8p LOH and 17q gain were promising indicators of survival in patients older than 5 years, and 1p, 4p, and 11q LOH potentially contributed to outcome prediction in the intermediate-risk group. Our genetic overview clarifies the clinical impact of genetic signatures and aids in the better understanding of genetic basis of neuroblastoma.