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Association between frequent CpG island methylation and HER2 amplification in human breast cancers.
Carcinogenesis. 2009 Mar; 30(3):466-71.C

Abstract

The presence of frequent methylation of CpG islands (CGIs), designated as the CpG island methylator phenotype in some cancers, is associated with distinct clinicopathological characteristics, including gene amplification, in individual tumor types. Amplification of HER2 in human breast cancers is an important prognostic and therapeutic target, but an association between HER2 amplification and frequent CGI methylation is unknown. To clarify the association, we here quantified methylation levels of promoter CGIs of 11 genes, which are unlikely to confer growth advantage to cells, in 63 human breast cancers. The number of methylated genes in a cancer did not obey a bimodal distribution, and the 63 cancers were classified into those with frequent methylation (n = 16), moderate methylation (n = 26) and no methylation (n = 21). The incidence of HER2 amplification was significantly higher in the cancers with frequent methylation (11 of 16) than in those with no methylation (2 of 21, P = 0.001). Also, the number of methylated genes correlated with the degree of HER2 amplification (r = 0.411, P = 0.002). Correlation analysis with clinicopathological characteristics and methylation of CDKN2A, BRCA1 and CDH1 revealed that frequent methylation had significant correlation with higher nuclear grades (P = 0.001). These showed that frequent methylation had a strong association with HER2 amplification in breast cancers and suggested that frequent methylation can be a determinant of various characteristics in a fraction of human breast cancers.

Authors+Show Affiliations

Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.No affiliation info availableNo 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

Language

eng

PubMed ID

19168584

Citation

Terada, Kotoe, et al. "Association Between Frequent CpG Island Methylation and HER2 Amplification in Human Breast Cancers." Carcinogenesis, vol. 30, no. 3, 2009, pp. 466-71.
Terada K, Okochi-Takada E, Akashi-Tanaka S, et al. Association between frequent CpG island methylation and HER2 amplification in human breast cancers. Carcinogenesis. 2009;30(3):466-71.
Terada, K., Okochi-Takada, E., Akashi-Tanaka, S., Miyamoto, K., Taniyama, K., Tsuda, H., Asada, K., Kaminishi, M., & Ushijima, T. (2009). Association between frequent CpG island methylation and HER2 amplification in human breast cancers. Carcinogenesis, 30(3), 466-71. https://doi.org/10.1093/carcin/bgp021
Terada K, et al. Association Between Frequent CpG Island Methylation and HER2 Amplification in Human Breast Cancers. Carcinogenesis. 2009;30(3):466-71. PubMed PMID: 19168584.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between frequent CpG island methylation and HER2 amplification in human breast cancers. AU - Terada,Kotoe, AU - Okochi-Takada,Eriko, AU - Akashi-Tanaka,Sadako, AU - Miyamoto,Kazuaki, AU - Taniyama,Kiyomi, AU - Tsuda,Hitoshi, AU - Asada,Kiyoshi, AU - Kaminishi,Michio, AU - Ushijima,Toshikazu, Y1 - 2009/01/23/ PY - 2009/1/27/entrez PY - 2009/1/27/pubmed PY - 2009/4/11/medline SP - 466 EP - 71 JF - Carcinogenesis JO - Carcinogenesis VL - 30 IS - 3 N2 - The presence of frequent methylation of CpG islands (CGIs), designated as the CpG island methylator phenotype in some cancers, is associated with distinct clinicopathological characteristics, including gene amplification, in individual tumor types. Amplification of HER2 in human breast cancers is an important prognostic and therapeutic target, but an association between HER2 amplification and frequent CGI methylation is unknown. To clarify the association, we here quantified methylation levels of promoter CGIs of 11 genes, which are unlikely to confer growth advantage to cells, in 63 human breast cancers. The number of methylated genes in a cancer did not obey a bimodal distribution, and the 63 cancers were classified into those with frequent methylation (n = 16), moderate methylation (n = 26) and no methylation (n = 21). The incidence of HER2 amplification was significantly higher in the cancers with frequent methylation (11 of 16) than in those with no methylation (2 of 21, P = 0.001). Also, the number of methylated genes correlated with the degree of HER2 amplification (r = 0.411, P = 0.002). Correlation analysis with clinicopathological characteristics and methylation of CDKN2A, BRCA1 and CDH1 revealed that frequent methylation had significant correlation with higher nuclear grades (P = 0.001). These showed that frequent methylation had a strong association with HER2 amplification in breast cancers and suggested that frequent methylation can be a determinant of various characteristics in a fraction of human breast cancers. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/19168584/Association_between_frequent_CpG_island_methylation_and_HER2_amplification_in_human_breast_cancers_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgp021 DB - PRIME DP - Unbound Medicine ER -