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CpG island methylator phenotype of multigene in serum of sporadic breast carcinoma

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Tumor Biology

Abstract

CpG island methylator phenotype (CIMP) involves methylation targeted toward the promoters of multiple genes. We determined a methylation profile of tumor-related genes in serum of sporadic breast cancer (SBC). The multigene methylation was examined by methylation-specific polymerase chain reaction assay in serum of 50 SBCs and 50 paired nontumors, and CIMP+ was defined as having three genes that are concordantly methylated. The methylation frequency of ten genes in serum of 50 SBCs varied from 10% in FHIT to 74% in RASSF1A. The methylation status of RASSF1A, BRCA1, p16, CDH1, ER, RARβ2, APC, and DAPK was significantly correlated with SBC and nontumor serum (P < 0.05). Methylation of at least one gene was found in 92% SBC; CIMP was more frequent in SBC than nontumor serum (P < 0.001). There was a significant association between CIMP and methylation of RASSF1A, BRCA1, p16, CDH1, ER, RARβ2, APC, and DAPK (P < 0.05); the methylation link profile of CDH1, RASSF1A, BRCA1, and RARβ2 as breast cancer marker may contribute high sensitivity (90%) and specificity (88%). ER and RARβ2 methylation was associated with elevated serum CA153 levels in 39 SBC samples with CIMP+ (P < 0.05). Multivariate analysis showed that living area of patients was found to provide independent prognostic information associated with a relative risk of tumor recurrence of 5.3. Multigene-specific methylation profile in serum was association with the recurrence risk of rural SBC, and positive correlation of CIMP can serve as a promising molecular marker of SBC.

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Grants provided by Science Funds for Distinguished Young Scholar of Hubei Province (2008154), Natural Science Foundation of Hubei Province (2007ABA371), Science Funds from Hubei Provincial Department of Education (Q20082407), and Innovation Foundation for Young Scholars of Yunyang Medical College (CXX200805).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Feng Jing & Hu Lihua

  2. Southern Medical University, Fengxian Hospital, Shanghai, China

    Feng Jing & Wang Yuping

  3. Taihe Hospital, Yunyang Medical College, Shiyan, China

    Chen Yong, Luo Jie, Lu Jun & Tang Xuanbing

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  1. Feng Jing
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  2. Wang Yuping
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  7. Hu Lihua
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Correspondence to Hu Lihua.

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Feng Jing and Wang Yuping contributed equally to this work.

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Jing, F., Yuping, W., Yong, C. et al. CpG island methylator phenotype of multigene in serum of sporadic breast carcinoma. Tumor Biol. 31, 321–331 (2010). https://doi.org/10.1007/s13277-010-0040-x

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