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Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas.

Abstract：

OBJECTIVE:The CpG island methylator phenotype is strongly associated with poor survival in neuroblastomas. Neuroblastomas with the CpG island methylator phenotype include almost all neuroblastomas with MYCN amplification, and, even among neuroblastomas without MYCN amplification, have worse prognosis. At the same time, methylation of individual tumor-suppressor genes is also reported to be associated with poor survival. The purpose of this study was to compare the prognostic power of the CpG island methylator phenotype with that of methylation of individual genes. METHODS:Methylation-specific polymerase chain reaction was performed for five individual genes (CASP8, EMP3, HOXA9, NR1I2 and CD44) in 140 Japanese and 152 German neuroblastomas. Kaplan-Meier analysis and log-rank tests were conducted to compare the survival between groups defined by methylation status. RESULTS:Among the five individual genes, only CASP8 methylation had a significant association with poor overall survival both in Japanese (hazard ratio = 3.1; 95% confidence interval = 1.5-6.4; P = 0.002) and German (hazard ratio = 4.8; 95% confidence interval = 2.1-11; P = 0.0002) neuroblastomas. HOXA9 and NR1I2 methylation were associated with poor survival only in German neuroblastomas. On the other hand, the CpG island methylator phenotype had a strong and consistent association in Japanese (hazard ratio = 22; 95% confidence interval = 5.3-93; P = 1.5 × 10(-5)) and German (hazard ratio = 9.5; 95% confidence interval = 3.2-28; P = 4.7 × 10(-5)) neuroblastomas. CONCLUSION:The CpG island methylator phenotype is likely to have stronger prognostic power than methylation of individual genes in neuroblastomas.

journal_name

Jpn J Clin Oncol

journal_title

Japanese journal of clinical oncology

authors

Asada K,Watanabe N,Nakamura Y,Ohira M,Westermann F,Schwab M,Nakagawara A,Ushijima T

doi

10.1093/jjco/hyt058

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

641-5

issue

6

eissn

0368-2811

issn

1465-3621

pii

hyt058

journal_volume

43

pub_type

杂志文章

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