title: Marked and independent prognostic significance of the CpG island methylator phenotype in neuroblastomas.
abstract: The CpG island methylator phenotype (CIMP) 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.
authors.affiliation: Carcinogenesis Division, National Cancer Center Research Institute, University of Tokyo Graduate School of Medicine, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Abe
authors.forename: Frank
authors.initials: F
authors.lastname: Westermann
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takato
authors.forename: Manfred
authors.initials: M
authors.lastname: Schwab
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis