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Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas.
Jpn J Clin Oncol. 2013 Jun; 43(6):641-5.JJ

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.

Authors+Show Affiliations

Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23619990

Citation

Asada, Kiyoshi, et al. "Stronger Prognostic Power of the CpG Island Methylator Phenotype Than Methylation of Individual Genes in Neuroblastomas." Japanese Journal of Clinical Oncology, vol. 43, no. 6, 2013, pp. 641-5.
Asada K, Watanabe N, Nakamura Y, et al. Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas. Jpn J Clin Oncol. 2013;43(6):641-5.
Asada, K., Watanabe, N., Nakamura, Y., Ohira, M., Westermann, F., Schwab, M., Nakagawara, A., & Ushijima, T. (2013). Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas. Japanese Journal of Clinical Oncology, 43(6), 641-5. https://doi.org/10.1093/jjco/hyt058
Asada K, et al. Stronger Prognostic Power of the CpG Island Methylator Phenotype Than Methylation of Individual Genes in Neuroblastomas. Jpn J Clin Oncol. 2013;43(6):641-5. PubMed PMID: 23619990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas. AU - Asada,Kiyoshi, AU - Watanabe,Naoko, AU - Nakamura,Yohko, AU - Ohira,Miki, AU - Westermann,Frank, AU - Schwab,Manfred, AU - Nakagawara,Akira, AU - Ushijima,Toshikazu, Y1 - 2013/04/25/ PY - 2013/4/27/entrez PY - 2013/4/27/pubmed PY - 2013/8/21/medline KW - CIMP KW - methylation KW - neuroblastoma KW - poor survival SP - 641 EP - 5 JF - Japanese journal of clinical oncology JO - Jpn J Clin Oncol VL - 43 IS - 6 N2 - 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. SN - 1465-3621 UR - https://www.unboundmedicine.com/medline/citation/23619990/Stronger_prognostic_power_of_the_CpG_island_methylator_phenotype_than_methylation_of_individual_genes_in_neuroblastomas_ L2 - https://academic.oup.com/jjco/article-lookup/doi/10.1093/jjco/hyt058 DB - PRIME DP - Unbound Medicine ER -