Marked and independent prognostic significance of the CpG island methylator phenotype in neuroblastomas

The CpG island methylator phenotype (ClMP) was closely associated with poor overall survival (OS) in Japanese neuroblastoma (NBL) cases in our previous study. Here, in German NBL cases, CIMP(+) cases (n = 95) showed markedly poorer OS (hazard ratio (HR) = 9.5; P < 0.0001) and disease-free survival (DFS) (HR = 5.4; P < 0.0001) than CIMP(-) cases (n = 50). All the 23 cases with N-myc amplification had CIMP. Among the remaining cases without N-myc amplification, CIMP(+) cases (n 27) had a poorer OS (HR = 4.5; P = 0.02) and DFS (HR = 5.2; P < 0.0001) than CIMP(-) cases (n = 95). In multivariate analysis, CIMP and N-myc amplification had an influence on OS and DFS independent of age and disease stage. CIMP had a stronger influence on DFS than N-myc amplification while N-myc had a stronger influence on OS. (c) 2006 Elsevier Ireland Ltd. All rights reserved.