CpG island methylator phenotype of multigene in serum of sporadic breast carcinoma.
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, RARbeta2, 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, RARbeta2, APC, and DAPK (P < 0.05); the methylation link profile of CDH1, RASSF1A, BRCA1, and RARbeta2 as breast cancer marker may contribute high sensitivity (90%) and specificity (88%). ER and RARbeta2 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.
Jing
Feng
F
Department of Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yuping
Wang
W
Yong
Chen
C
Jie
Luo
L
Jun
Lu
L
Xuanbing
Tang
T
Lihua
Hu
H
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000097:blood / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm